A Quick Look at Biochemistry Lipid Metabolism 2155 6156.1000324

Dashty, J Diabetes Metab 2014, 5:1
Diabetes & Metabolism http://dx.doi.org/10.4172/2155-6156.1000324
Review Article Open Access
A Quick Look at Biochemistry: Lipid Metabolism

Monireh Dashty
Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands
Abstract
Lipids and carbohydrates are the energetic molecules and one of the main components of the metabolic system.
These molecules circulate in the blood stream and between the metabolic tissues and transfer energy throughout
the body. They are degraded and release their energy in the form of adenosine triphosphate (ATP) to be used in
anabolic reactions. Anabolic reactions are the energy consumer reactions for synthesis of molecules or energy
storage. These include glycogenolysis, glycolysis, tricarboxylic acid (TCA, citric acid or the Krebs) cycle, electron
transfer chain, fatty acid beta oxidation and protein breakdown. Carbohydrates are the main energetic molecules
that are consumed by active tissues like muscles. In excess consumption of carbohydrates, they are converted to
lipid molecules to be stored in the adipose tissue for the time of starvation. This matter is one of the most important
functions of the body in energy homeostasis. In this review, the main lipid groups are introduced and fat biochemical
pathways are highlighted and illustrated in a way to facilitate follow up of the lipid biochemical pathways and to give
the reader a better understanding of the pathogenesis of metabolic system disorders.
Keywords: Lipid; Carbohydrate; Lipoprotein; Atherosclerosis are not soluble in water. Oil is also used for any substance that does not
mix with water and has a greasy feel regardless of its chemical structure,
Introduction for instance petroleum, heating oil, and essential oil.
Lipids are a group of naturally occurring compounds and Fats are an important part of the diet and are broken down by
hydrophobic or amphiphilic molecules that form structures such as lipases and serve both structural and metabolic functions. They play
vesicles, liposomes or membranes in an aqueous environment. They a vital role in energy storage in the body, health of skin and hair [2],
are a large and diverse group of organic macromolecules; hence, it is promoting cell function and protecting body organs against shock and
always difficult for scientists to provide a specific definition for the word maintaining body temperature. They are sources of essential FAs and
lipid. Therefore, due to the absence of a widely-accepted definition are required for the function of fat-soluble vitamins (A, D, E and K). The
in this regard, lipids are categorized based on their different chemical new fat tissues also function to dilute unsafe levels of substances in the
properties including their ability for saponification, their chemical bloodstream by storing them in their adipocytes. This helps to protect
compositions and their building blocks. Saponification is the ability vital organs until the substances can be metabolized and/or removed
of lipids to be hydrolyzed by basic solutions into compounds such as from the body. It is also a useful buffer towards a host of diseases [3].
glycerol and fatty acids (FAs). Based on their chemical composition,
lipids are classified into simple and complex lipids. Simple lipids contain Fatty acids
one or two different types of compounds. However, complex lipids FAs (CnCOOH) are amphipathic hydrocarbon chain molecules
frequently consist of three or more chemical identities (e.g., glycerol, synthesized using acetyl-CoA and malonyl-CoA. They are terminated
FAs, and sugar) and they are usually amphipathic. Based on their with a polar, hydrophilic carboxylic acid end and a non-polar,
building-blocks, lipids are categorized into two ketoacyl and isoprene hydrophobic end that is insoluble in water. They usually have an even
groups. In this categorization, lipids with ketoacyl subunits are divided
number of carbon atoms. FAs are used in other complex lipids and
into eight categories including FAs, glycerolipids, glycerophospholipids,
may be attached to functional groups containing oxygen, nitrogen,
sphingolipids, saccharolipids, and polyketides while sterol lipids and
halogens and sulfur. Biologically important FAs are eicosanoids,
prenol lipids derived from isoprene subunits. Regardless of all diversities
docosahexaenoic acid, fatty esters and fatty amides. Eicosanoids
in lipid classification, overlapping between different classifications still
include prostaglandins, leukotrienes, thromboxanes, which are derived
exist. This section simply introduces definitions of each category that
primarily from arachidonic acid and eicosapentaenoic acid. Fatty esters
is described in general books [1]. Nomenclatures, abbreviations and
include wax esters, FA thioester coenzyme A derivatives, FA thioester
formulas are explained in the text and figures 1 and 2.
acyl carrier protein (ACP) derivatives and FA carnitine. Fatty amides
Lipid Categorization and their Definitions
In this section a general definition of lipids, fats and oils is required
that the differ between these terminologies be clarified. Fats consist of *Corresponding author: Monireh Dashty, Department of Cell Biology, University
a wide group of compounds with the same chemical structure that are Medical Center Groningen, University of Groningen, Antonius Deusinglaan 1,
9713 AV, Groningen, The Netherlands, Tel: +31 (0) 50 3632536; Fax: +31 (0) 50
derivatives of FAs and glycerol bounded together via ester bonds. 3632522; E-mail: M.Dashti.Rahmatabadi@med.umcg.nl
For instance, triglycerides are triesters of glycerol with three FAs. The
Received November 26, 2013; Accepted January 02, 2014; Published January
properties of fats depend on their structure and particularly on the 07, 2014
composition of their FAs. Long chain FAs (LCFAs) yield more energy
per molecule during degradation and have a higher melting point Citation: Dashty M (2014) A Quick Look at Biochemistry: Lipid Metabolism. J
Diabetes Metab 2: 324. doi:10.4172/2155-6156.1000324
compared to short chain FAs. Therefore, fats may be either solid or
liquid at room temperature. Oils are referred to fats that are liquid at Copyright: 2014 Dashty M. This is an open-access article distributed under the
terms of the Creative Commons Attribution License, which permits unrestricted
normal room temperature, while fats are usually solid at normal room use, distribution, and reproduction in any medium, provided the original author and
temperature. Lipids is used to refer to both liquid and solid fats that source are credited.
J Diabetes Metab
ISSN: 2155-6156 JDM, an open access journal Volume 5 Issue 1 1000324
Citation: Dashty M (2014) A Quick Look at Biochemistry: Lipid Metabolism. J Diabetes Metab 2: 324. doi:10.4172/2155-6156.1000324
Page 2 of 19
Figure 1a: Abbreviations. Figure 1b: Abbreviations.
J Diabetes Metab
Page 3 of 19
saturated fats are typically solid at room temperature, while highly

unsaturated fats are oily.
Acylglycerols (AGs)
Acylglycerols (glycerolipids, glycerides or neutral fats) are glycerol
esters of FAs. Esterification of one, two or three FAs with glycerol yield
monoacylglycerol (MAG), diacylglycerol (DAG) or triacylglycerol
(TAG) respectively. TAGs function as energy store in the adipose
tissues that are hydrolyzed to release glycerol and FAs for consumption
of their energy in the shortage of energy. The other molecules in this
category are glucosylglycerol (such as digalactosyldiacylglycerol and
seminolipid), which are molecules composed of sugar residues and
glycerol.
Waxes
Waxes are saponificable, very hydrophobic compounds that
are biosynthesized by many plants and animals. They are formed by
esterification of long chain FAs (alkyl groups) with hydroxyl group of
long chain fatty alcohols or lipid alcohols such as sterols, aminoalcohols,
hydroxycarotenoids or terpenols. They are organic compounds that are
plastic near ambient temperatures. Above 45C, they melt to produce
a low viscosity liquid. Natural waxes are a mixture of waxes and other
substances such as hydrocarbons, fatty alcohols, fatty aldehydes, FAs,
terpenes, etc, that form a protective coating in plants and animals
against desiccation and parasites. Synthetic waxes are long-chain
hydrocarbons lacking functional groups.
Phospholipids
Phospholipids are complex lipid molecules in which phosphate
group attaches to one alcohol that may be linked to fatty chains.
Phospholipids are the major structural constituents of all biological
membranes because they tend to form lipid bilayers corresponding to
their ionic head and hydrophobic tails. They also may be involved in
signal transduction. Phospholipids are classified into two main groups:
glycerophospholipids and sphingosyl phosphatides.
Glycerophospholipids are amphipathic molecules that are formed
by esterification of an alcohol to the phosphate of phosphatidic
acid (1,2 diacylglycerol 3-phosphate). They are found in the neural
tissue and lipid bilayer of cell and function in metabolism and cell
signaling. They are subdivided into phosphatidylcholine (PC or
lecithin), phosphatidylethanolamine (PE), phosphatidylserine (PS),
Figure 2: Formulae. Abbreviations are explained in figure 1.
phosphatidylinositols (PI), phosphatidylglycerol (PG) and cardiolipin
or diphosphatidylglycerol (DPG). Plasmalogens are a group of
include N-acylethanolamines, such as cannabinoid neurotransmitter phospholipids in whose structure one fatty aldehyde is substituted by
anandamide. the FA. Therefore, they are phosphatidyl molecules that are linked to
ethanolamine, choline, serine or inositol. Glycerophospholipids can be
Chemically, FAs are categorized into saturated and unsaturated
hydrolyzed by phospholipases or by alkaline solutions.
forms. In saturated FAs (CnH(2n+1)COOH), their carbon chain is
saturated with hydrogen during hydrogenation process. Unsaturated Sphingosyl phosphatides are lipids containing (sphingo)ceramides
FAs (CnH(2n-1)COOH) contain double bonds within their carbon linked by their hydroxyl group to a phosphate group, itself esterified
chain. Monounsaturated FAs (MUFAs) have only one double bond to a polar head group such as choline (in sphingomyelins (SMs)),
and polyunsaturated FAs (PUFAs or polyenoic FAs) contain two or ethanolamine and glycerol or to a glycoside moiety (in glycolipids)
more double bonds. Unsaturated fats can be further divided into Cis
or Trans geometric isomers, which significantly affect the molecules Sphingolipids
configuration, structure and function of cell membranes. Most naturally Sphingolipids comprise a complex range of lipids in which FAs are
occurring FAs are of the Cis configuration, while Trans configuration linked via amide bonds to a long-chain base or sphingoid. A sphingoid
significantly increases the risk of coronary heart disease. Saturated and base backbone is synthesized from serine and a long-chain fatty acyl-
unsaturated forms differ in their energy content and melting point. CoA (palmitoyl-CoA). The major sphingoid base of mammals is
Energy that is yielded during metabolism of unsaturated fats is less than commonly referred to as sphingosine. Some sphingoid base derivatives
that of saturated fats with the same number of carbon atoms. Moreover, are ceramides, SM (a phosphosphingolipids) and glycosphingolipids.
J Diabetes Metab
Page 4 of 19
Ceramide is a product that is yielded by amide-linkage of FA to the and dimethylallyl diphosphate that are produced mainly via the
sphingosine molecule. Combination of ceramide with one molecule mevalonic acid (MVA) pathway. The simple isoprenoids (linear
of phosphocholine produces SM (or ceramide phosphocholine). alcohols, diphosphates, etc.) are formed by the successive addition
Glycosphingolipids are molecules composed of one or more sugar of C5 units and are classified according to the number of these
residues linked to the sphingoid base via a glycosidic bond. Examples terpene units. Polyterpenes are structures containing greater than
of glycosphingolipids are cerebrosides, globosides and gangliosides. 40 carbons. Carotenoids are important simple isoprenoids that
Cerebrosides are made by glycosidic linkage of the hydroxyl group function as antioxidants and as precursors of vitamin A. Another
of ceramide with one hexose molecule (glucose or galactose). In biologically important class of molecules is exemplified by quinones
globosides one hexose molecule is substituted with dimmers. The and hydroquinones, which contain an isoprenoid tail attached to a
molecular structures of gangliosides are similar to cerebrosides. It has quinonoid core of non-isoprenoid origin. Vitamin E and vitamin K, as
at least three sugars, one of which must be sialic acid. Sphingolipids well as ubiquinones, are examples of this class.
protect the cell surface against harmful environmental factors.
Certain complex glycosphingolipids are involved in cell recognition Saccharolipids
and signaling. Ceramide and sphingosine-1-phosphate are important Saccharolipids are compounds in which FAs are linked directly
mediators in the signaling cascades involved in apoptosis, proliferation, to a sugar backbone. In saccharolipids, a monosaccharide substitutes
stress responses, necrosis, inflammation, autophagy, senescence, and for the glycerol backbone of glycerolipids and glycerophospholipids.
differentiation. In experimental animals, feeding sphingolipids inhibits The most familiar saccharolipids in Gram-negative bacteria are the
colon carcinogenesis, reduces low-density lipoprotein (LDL) cholesterol acylated glucosamine precursors of the Lipid A component of the
and elevates high-density lipoprotein (HDL) cholesterol. lipopolysaccharides (LPS).
Terpenes Polyketides
Terpenes are lipids with the building blocks of isoprene units Polyketides are synthesized by polymerization of acetyl and
(2-methyl 1,3-butanodiene, C=C(C)-C=C). Isoprene units may be propionyl subunits by classic enzymes as well as iterative and
linked in a head to tail or in a head to head fashion, and the resulting multimodular enzymes that share mechanistic features with the FA
compounds can be cyclic or acyclic, and saturated or unsaturated. synthases. They comprise a large number of secondary metabolites
Terpenes are classified depending on the number of isoprene units and natural products from animal, plant, bacterial, fungal and marine
incorporated into the basic molecular skeleton. Many terpenes are sources, and have great structural diversity. Many polyketides are
hydrocarbons, although oxygen-containing compounds such as cyclic molecules whose backbones are often further modified by
alcohols, aldehydes or ketones (terpenoids) are also found. Moreover, glycosylation, methylation, hydroxylation, oxidation, and/or other
isoprene units are also found within the framework of certain phenols processes. Many commonly used anti-microbial, anti-parasitic, and
(quinones) and indole alkaloids. Terpenes are probably the most anti-cancer agents are polyketides or polyketide derivatives, such as
widespread group of natural products such as essential oils, resins, tetracyclines, erythromycins, avermectins, and antitumor epothilones.
waxes, rubber, carotenoids, etc. They are also involved in the synthesis
of steroids, vitamins, and chlorophyll, as well as in the acylation of Cyanolipids
proteins. Cyanolipids are made with FAs esterified to mono- or dihydroxy
Steroids nitrile moieties. Cyanolipids are mainly found in cyanobacteria and
plants, and their hydrolysis usually produces hydrogen cyanide (HCN),
Steroids are modified triterpenes derived from squalene. They which has a protective effect.
are lipid compounds based on the fundamental saturated tetracyclic
hydrocarbon 1,2-cyclopentanoperhydrophenanthrene (sterane or Phenolic lipids
gonane), which can be modified by C-C bond scissions, ring expansions Phenolic lipids are mainly present in plants, fungi, and bacteria.
or contractions, dehydrogenation, and substitutions. Examples of This heterogeneous group includes simple phenols and polyphenols as
steroids are estrogen, progesterone, androgens (testosterone and well as their derivatives, and can be classified into coumarins, quinones,
androsterone), glucocorticoids and mineralocorticoids and they have flavonoids and phenolics. They have a wide range of biological effects
biological roles as hormones and signaling molecules. including antimicrobials, antioxidants, toxics, enzyme inhibitors, etc.
Sterols are steroid alcohols or steroids with a hydroxyl group in the The single-ring lipid compounds are made up of a catechol, a resorcinol
3-position of the A-ring. Sterols form part of the cellular membrane or a hydroquinone nucleus alkylated by a variable non-isoprenoid
where they influence their fluidity and function and participate in carbon chain.
developmental signaling as secondary messengers. The most important
Lipids containing aminocompounds
sterols are cholesterol, which is an important component of membrane
lipids, along with the glycerophospholipids and SMs. Other examples These compounds are made of linking FAs with the substances that
of sterols are bile acids and their conjugates, which in mammals are contain amino groups. They are classified as (i) aminoalcohols, (ii)
oxidized derivatives of cholesterol and are synthesized in the liver. ceramides, (iii) lipoamino acids and lipopeptides and others like (iv)
Secosteroids, comprising different forms of vitamin D, are characterized acyl-CoAs (thioester bond), acyl carnitines (ester bond) and dopamine
by cleavage of the B ring of the core structure. Steroids are important (amide bond). Aminoalcohols are long carbon chains containing
components of cell membranes, hormones and vitamin D precursors. one or more alcohol groups and one amino group synthesized by
condensation of an amino acid and an acyl-CoA. Aminoalcohols can
Prenol lipids be saturated or unsaturated, linear or branched and can have additional
Prenol lipids are compounds that are synthesized from the five- groups like ethanolamine, choline, and sphingosine. The most common
carbon-unit precursor isopentenyl di(or pyro)phosphate (IPP) aminoalcohols are sphingosine and their derivatives. Ceramides are
J Diabetes Metab
Page 5 of 19
the simplest sphingolipids that result from the condensation of an

aminoalcohol and a FA through an amide bond (when the condensation
is through an ester bond the result is a wax). Free sphingoceramides
are found in some tissues or are involved as messenger molecules,
although their alcohol function is frequently linked to a glucide
(glycosphingolipids) or is esterified by a phosphoric acid linked to
a polar group (SMs). Another important group of ceramides are
N-acylethanolamines (NAEs). Lipoamino acids and lipopeptides are
amphipathic membrane lipids composed of one amino acid (lipoamino
acids) or more amino acids (lipopeptides) linked to a FA through an
amide bond. A second FA can be linked to the amino acid through an
ester bond. They may act as virulence factors, or have pharmacological
activity (e.g., lipstatin is a lipase inhibitor used against obesity).
Glycolipids Figure 3: The structure of adipose tissue
Adipose tissue is composed of some cells including adipocytes, fibroblasts,
Glycolipids are complex membrane lipids containing a glycosidic endothelial cells, macrophages and stem cells. Adipocyte is the main cell of
moiety. They are classified into (i) glycosides of FAs, lipid alcohols and adipose tissue that is mainly composed of a nucleus and a large lipid droplet in
steroids, (ii) glyceroglycolipids or glycolipids based on glycerol, (iii) mature adipocytes surrounded by a cytoplasmic membrane. The structure of a
lipid droplet is similar to lipoproteins.
glycosphingolipids or glycolipids based on ceramides, (iv) glycosides
of lipoamino acids or lipoamino acids containing glycosyl moieties and
(v) LPS.
Lipids of group (i) are made up of linking a glycosyl moiety (one
or several units) to one or more FAs, fatty alcohols, and alkyl chains.
Lipids of group (ii) consist of a mono-, di-, or oligosaccharide moiety
that via the glycosidic bonds links to the hydroxyl group of glycerol,
which may be acylated (or alkylated) with one or two FAs. Furthermore,
these glycolipids may contain additional groups and chains. They form
compounds such as lipoteichoic acids (LTA) of Gram-positive bacterial
membranes, which consist of polymers of glycerol-1-phosphate linked
to a (phosphatidyl) glycosyl diglyceride. Lipids of group (iii) are a
mono-, di-, or oligosaccharide moiety linked to the hydroxyl group of
a ceramide backbone. The ceramide and the glycosyl group(s), which
can be neutral (unsubstituted) or acidic (substituted with carboxyl,
sulphate or phosphate group(s)), can have further modifications. The
best known ones are cerebrosides (a ceramide linked to a hexose) and Figure 4: Comparison between structural similarity between lipoproteins and
adipocytes-LDs
gangliosides (a ceramide linked to an oligosaccharide containing sialic Both the lipoprotein particles and adipocytes-LDs compose of an external lipid
acid). Lipids of group (iv) including lipids having an amino acid with layer consist of phospholipids and cholesterol that covers the central lipids
N-acyl and/or ester linkages and lipids having a glycerol and an amino of particles. Apolipoproteins are assembled in the phospholipid layer and are
acid with ether linkage. LPS are the endotoxic O-antigens found in unique among these particles.
outer membranes of Gram-negative bacteria. The lipid part (Lipid A)
is responsible for the toxic activity of these bacteria and septic shock triacylglycerol (TAG, triacylglyceride or triglyceride) as the source of
and comprises of a backbone of -1,6-glucosaminyl-glucosamine. The energy in the body; hence, they are biologically active molecules.
3-position of glucosamine II establishes a glycosidic linkage with a
long-chain polysaccharide. The other hydroxyl and amine groups are Membranes
substituted with normal or hydroxy FAs. A biological membrane is a form of lipid bilayer in an aqueous
Proteolipids system, in which the polar heads of lipids align towards the polar
aqueous environment, while the hydrophobic tails tend to cluster
Proteolipids or fatty acylated proteins are proteins that contain one together, forming a vesicle, micelles, liposomes, or lipid bilayers
or more covalently associated acyl moieties. Proteolipids are divided depending on the concentration of the lipid. The glycerophospholipids,
into (i) myristoylated proteins in which myristic acid is bound by amide SM and sterols (mainly cholesterol) are the main structural components
linkage to glycine residue of the protein and (ii) palmitoylated proteins of biological membranes.
in which palmitic acids (or other long FAs) are bound by thioester
linkages to cysteine residues of the protein. Acylation is one of the most Energy storage
widespread modifications of cytosolic and membrane proteins in all Triglycerides are a major form of energy storage in adipose tissues.
living things and can direct soluble proteins to membranes. The complete oxidation of FAs provides about 9kcal/gram energy that
is higher than that produced from the breakdown of carbohydrates and
Biological Functions of Lipids proteins (4kcal/gram).
Fats are one of the main components of the body which are involved
in many different functions. Mainly, they function in the structure of
Signaling
cell membrane and they are stored in adipose tissue in the form of Lipid signaling is a vital part of cell signaling. Lipid signaling
J Diabetes Metab
Page 6 of 19
may occur via activation of G protein-coupled receptors (GPCRs) which is the intermediate molecule of glucose oxidation process, to
and members of lipid categories as signaling molecules and cellular be used in the mitochondrial oxidative phosphorylation (OXPHOS)
messengers. These include sphingosine-1-phosphate, diacylglycerol reaction and release their energy. Therefore, there is a close interaction
(DAG), PI phosphates (PIPs), PS, prostaglandins, steroid hormones between lipid and carbohydrate pathways in cells. On the one hand,
such as estrogen, testosterone, cortisol and oxysterols such as excess of carbohydrates in the body is reserved in the form of neutral
25-hydroxycholesterol. lipids such as cholesterol esters, TAG or FA. In shortage of available
energy in the form of carbohydrate, lipolysis is increased via FA
Other functions oxidation (FAO) to produce acetyl-CoA to be used in the carbohydrate
The fat-soluble vitamins (A, D, E and K), which are isoprene- pathways. This capacity of the body, which is nutritional storage in the
based lipids, are essential nutrients stored in the liver and adipose form of lipids in the feeding state for usage in the form of carbohydrates
tissues, with a diverse range of functions. Acyl-carnitines are involved in the starvation state, is one of the fundamental capacities of living
in the transport and metabolism of FAs in and out of mitochondria things and is essential for life.
during beta oxidation. Polyprenols and their phosphorylated derivatives Lipid storage in the body happens normally in the white adipose
also play important roles in transport of oligosaccharides across tissue (WAT). Therefore, structurally the main cytoplasmic organelles
membranes. Polyprenol phosphate sugars and polyprenol diphosphate of WAT-adipocytes consist of a nucleus and a (in mature adipocyte)
sugars function in extracytoplasmic glycosylation reactions, in or lots of (in small adipocytes) functional lipid organelles for
extracellular polysaccharide biosynthesis (for instance, peptidoglycan sequestration of extracellular lipids (Figure 3) [14]. The number and
polymerization in bacteria), and in eukaryotic protein N-glycosylation. activity of mitochondria in this tissue is not high. These lipid organelles
Cardiolipins are a subclass of glycerophospholipids containing four acyl that are also called lipid droplets (LDs) have almost the same structural
chains and three glycerol groups that are particularly abundant in the properties as lipoproteins (Figure 4). They have an external layer
inner mitochondrial membrane. They are believed to activate enzymes of phospholipids that covers the intra-organelle TAGs. LDs exist in
of oxidative phosphorylation reaction. different organs, namely skeletal muscle, liver and pancreas; however,
Fats and their Importance in the Pathogenesis of in adipose tissue they are highly specialized for lipid storage [14].
Metabolic Disorders Carbohydrates are the energetic molecules that the body directly
consumes in starvation and because of their solubility and availability
Fats and carbohydrates are the energetic molecules of the body. have a strong influence on the metabolic system of the body. The
This point highlights the metabolic functionality of these molecules in required energy of the body is produced either directly via degradation
the body. However, lipids and carbohydrates have different biophysical of carbohydrates or indirectly via nicotinamide adenine dinucleotide
properties; therefore, they influence the metabolic system of the body (NADH2) and flavin adenine dinucleotide (FADH2) oxidation during
in different ways. Lipids are insoluble particles in the watery based the OXPHOS reaction. Therefore, functional mitochondria are one of
circulation that require transporters for transfer. Transporters are the fundamental parameters in proper cellular metabolism, mainly in
soluble particles such as vesicles, endoplasmic reticulum (ER), the the catabolic tissues such as hepatocytes and myocytes. Skeletal muscles,
Golgi apparatus, intracellular lipid droplets and intra-circulatory which require a huge amount of energy for movement, have highly
lipoproteins [4,5]. These particles are made from lipids and proteins functional mitochondria. In expert athletes, LDs of the skeletal muscles
that influence the function of the particles; therefore, each particle that are in close contact with mitochondria are expanded to store a high
has different biological functions in the body. However, carbohydrates level of intramuscular triglyceride (IMTG). Athletes muscle cells have
are soluble crystal molecules that do not need carriers for transport. high insulin sensitivity that could be because of this close functional
Both the carbohydrates and lipids influence blood viscosity, which proximity between the mitochondria and the LDs as well as the high
has a significant effect on pathological events [6-8]. The change of ability of their LDs for intracellular-lipid sequestration [14]. In contrast,
viscosity affects cytoskeleton function and movement of intracellular during physiological obesity the concentration of glucose and free FAs
organelles [9] and as an environmental factor changes gene expression (FFAs) in circulation and consequently the metabolic functionality of
pattern of cells [10-12]. Furthermore, viscosity has a shear stress metabolic tissues will increase to storage the excess energy level of the
effect in the circulation and together with constituents of the lipid body in the form of triacylglycerol in their LDs. This leads to increase
particles influences the cardiocerebrovascular function [7]. During in the function of mitochondria for OXPHOS reaction of the energetic
atherosclerosis, the environmental hyperviscosity could enhance compounds of acetyl-CoA (product of both lipid and carbohydrate
atherothrombosis via influence on the membrane stretch [13]. degradation). In the pathological obesity state, mitochondrial
With regard to biochemistry, lipids have almost double energy dysfunction lead to FAO reduction, lipotoxicity in the cytoplasm, ER
than carbohydrates and are considered as the energy storage molecules stress and metabolic disorders [15-18]. In mitochondrial dysfunction,
in the form of TAG in adipose tissues. Therefore, the main function the amount of heat increases. Heat generation happens due to the high
of adipose tissue is the lipid storage capacity and not the catabolic amount of ATP production following OXPHOS reaction as well as the
function. Storage of energy in the form of TAG in adipose tissues is the leaky membrane of the inner mitochondrial membrane (IMM) during
best way for energy reservation in comparison with glycogen storage ATP production. In obese adults, the mass and function of the brown
in the skeletal muscles and liver because of three reasons. Firstly, fats adipose tissue (BAT) are strongly low. Activated BAT could have a great
produce 9.3 kcal/gram, while this amount for carbohydrates is 4 kcal/ effect in alleviation of the metabolic disorders during obesity [19].
gram. Secondly, lipid storage in adipose tissues requires less water than BAT increases energy expenditure and weight loss and improves lipid
carbohydrate storage in the form of glycogen. Therefore, compared to and glucose homeostasis. Therefore, active BAT is able to uptake large
the glycogen storage in skeletal muscle and liver the weight of adipose quantities of lipid and glucose from the circulation [20]. Moreover, each
tissues is less than the amount of energy which is reserved in it [14]. ATP produces 8 kcal that is 20% of its total energy and the rest of the
Finally, the body cannot use the energy of lipids directly in the metabolic energy is wasted as heat to maintain body temperature. In obesity state,
pathways. For this purpose, lipids should be degraded to acetyl-CoA, there is also defect in LD degradation and TAG lipolysis due to the low
J Diabetes Metab
Page 7 of 19
of glycerol. Fifty percent of TAG degradation happens by pancreatic

lipases that separate sequentially the acyl root (or FA) of the two outer
positions (1 and 2) of the glycerol carbon groups of TAGs and
produce monoglyceride. PLA2 is able to split off the FA of the middle
position () of the glycerol carbon group of monoglycerides and release
glycerol in 40% of TAG degradation. Ten percent of the TAGs can be
directly absorbed from the intestine cells to the circulation.
There are different hormones in the small intestine that can
affect fats. These hormones are (i) secretin and gastrin that stimulate
secretion of pancreatic electrolytes, (ii) pancreozymin that stimulates
the secretion of pancreatic lipase to degrade lipids and TAGs and (iii)
cholecystokinin that causes contraction of gall bladder for entrance of
bile salts in the duodenum.
Monoglycerides, following absorption in the intestinal enterocytes,
are assembled again to produce TAGs. Heavy lipids such as LCFAs,
TAGs, monoglyceride, DAGs, phospholipids and cholesterols enter the
bloodstream via the lymphatic vessels. Short-chain FAs directly enter
the circulation and form a complex with albumin and enter the liver via
the portal vein [24].
In intestinal cells, lipids are used for chylomicron (CM) assembly
and are then released to the lymphatic vessels and circulation. CMs
have a bipolar external monolayer that covers the hydrophobic internal
lipids. In the endothelial cells of tissues, they become degraded via
lipoprotein lipase (LPL) and their FAs enter the liver cytoplasm for
FAO.
Retour of External Cholesterol in the Body

Most of the external cholesterol is in the form of free cholesterol,
which is the form that can be absorbed by the enterocytes. Therefore,
esterified cholesterol loses its FA using cholesterol esterase and is
converted to the free form. Inside the enterocytes, the free cholesterol
becomes esterified again and are assembled together to form CMs,
which enter the bloodstream via lymphatic vessels. In circulation,
CMs are degraded by LPL and the esterified cholesterol enters the liver
via the portal vein and converts to free cholesterol. Eighty percent of
cholesterol in the liver is stored in the gallbladder in the form of bile
Figure 5: Comparison between the structures of lipoproteins
There is a reverse correlation between the size and density of lipoproteins
salts and 20% is used for generation of other cholesterol-based products
that represent the percentage of the lipids and proteins in these particles. For like sex hormones, phospholipids, CMs, cell membrane lipids, and
instance, HDL has the highest density (and protein percentage) and conversely vitamin D3. Cholesterol is released from the gallbladder to the intestine
the lowest size (and lipid percentage).
and is again absorbed via enterocytes.
level of adipose triglyceride lipase (ATGL) gene expression in skeletal Lipoproteins

muscles [21,22]. This matter increases the level of their bioactive lipid The aqueous environment of the body poses problems with the
species such as diglyceride (or diacylglycerol, DAG) and ceramides that transport of the hydrophobic substances between organs. Hence, animals
is known as lipotoxicity [22]. TAG accumulation in glycolytic muscles have evolved plasma lipoproteins that facilitate transport of TAGs and
can induce FA-induced insulin pathway disturbance or (FAID) [14]. cholesterol between the liver, adipose compartment and tissues [25].
Originally these structures were not thought to be of major importance
Origin of Fats and Lipid Uptakes
for transmitting endocrinologically relevant signals, but this view is
Fats originate from the external (TAG, cholesterol and now changing. In 2006, Panakova and colleagues [26] showed that
phospholipids of food) and internal parts of the body (TAG and lipophorin (the Drosophila equivalent of very low-density lipoprotein
cholesterol storages of adipose tissues and lipoproteins). In the external (VLDL) in mammals) carried hydrophobic ligands activating Wnt
origin, lipid solubilization (or emulsification) in the intestine happens signaling and Hedgehog morphogen pathways and these effects
by lipophilic bile acids, which are synthesized from cholesterol in the were physiologically highly relevant in the model organism, whereas
liver. This process renders fats accessible to the lipases. Fat digestion Queiroz et al. have shown that the morphogen is carried by lipoproteins
starts from the stomach by gastric lipase, which is active and stable in humans as well [27-29]. Interestingly, it has been recently reported
in acidic environments [23]. The main part of lipid degradation takes that vitamin D resides in LDL and that this is relevant for modulating
place in the small intestine and via steapsin or pancreatic lipase and signaling in atherosclerotic plaques [30,31]. Apart from hydrophobic
pancreatic phospholipase A2 (PLA2). These lipases affect TAGs, which morphogenes, other hydrophobic signaling molecules may also reside
are produced via esterification of three FAs with the carbon backbone in lipoproteins. Many hormones are highly hydrophobic and evidence
J Diabetes Metab
Page 8 of 19
is available that lipoproteins may be involved in their efficient transport and assembled with apoB48, apoA-I, apoA-II and apoA-IV to make
through the body. In ApoE-/- mice for instance, both endocannabinoid the nascent chylomicron (nCM), which is secreted to the lymphatic
[32] and glucocorticoid [33] signaling is disturbed and is strongly vessels (via its apolipoproteins) and released directly (bypass liver) to
associated with inflammation, insulin unresponsiveness and hepatic the circulation via the subclavian vein. In the circulation, HDL delivers
steatosis, suggesting that endocannabinoid carrying by lipoproteins its apolipoproteins (apoC-II and apoE) to the nCM to make mature
is a relevant process. Thus the lipoprotein compartment may have an chylomicron (mCM). These exchangeable apolipoproteins protect the
underestimated role in the human endocrinology. TAG-rich lipoprotein particles (CM and VLDL) from non-specified
interaction with the plasma and lead to their correct configuration for
Lipoprotein constituents the action of LPL. In the skeletal muscle and AT, mature chylomicron,
Lipoproteins are biochemical transporters that are composed of via activation of the endothelial LPL in the presence of phospholipids
proteins and lipids. The main function of lipoproteins in the body is and its cofactor apoC-II, ensures the hydrolysis of TAG to glycerol and
transport of lipids through the circulation from the sources of lipids FAs to be consumed or stored by tissues. Glycerol is returned to the
such as the intestine and liver to other tissues that require these fats liver and kidney to be converted to the glycolytic intermediates and
as their energy suppliers or use them as structural materials in their the phospholipid and apoA and apoC of mCM is transferred to HDL.
membrane. Their structure consists of an amphipathic monolayer of The hydrolyzed chylomicron, known as remnant chylomicron (rCM),
lipids, which is composed of an assembly of hydrophilic head groups contains cholesterol esters, apoE and apoB48. rCM is transferred
of phospholipids and free (non-esterified) cholesterol together with to the liver through the circulation, which in turn rCM ends up
apolipoproteins (apo) that face the aqueous phase and cover the intra with endocytosis mediated by the interaction of apoE with the rCM
hydrophobic (non-polar) part of their structure which are TAGs receptors in the hepatocytes [38,41-44]. Ultimately, rCM is degraded in
and cholesterol esters [34]. The polarity of the surface lipoproteins lysosome, which results in release of FAs and glycerol [41].
prevents their aggregation and allows them to be solubilized in the In the endogenous pathway, liver is the main source of VLDL lipid
circulation [35]. Lipids of the lipoproteins are TAG, free cholesterol, constituent. The assembly of intracellular TAG and cholesterol in the
cholesterol esters, and phospholipids like PC, PE, PI and SM [25]. liver is maintained by apoB100 and delivered to the circulation by
The particle proteins, via their interactions with each other and also lipid transporters [40,45]. Similar to CMs, circulating HDL provides
with other proteins including enzymes and the cell surface proteins, apoE and apoC-II to VLDL [46,47]. VLDLs contain TAG, cholesterol,
determine whether the lipids should be absorbed from or exported to cholesteryl ester, apoB-100, apoC-I, apoC-II, apoC-III and apoE. Thus,
particular tissues. The overall metabolism and structure of lipoproteins VLDL plays an important role in the delivery of FFA to the adipose
is determined by apolipoproteins and also the interactions with the tissue to store energy as inactive fuel in the form of TAGs in the
peripheral receptor molecules [36,37]. The main categorization of adipocytes-associated LDs or supply active energy for skeletal muscles
lipoproteins is based on their diameter and density as well as their and other tissues via FFA delivery [45]. LPL ensures release of FAs and
proteins and lipids compositions. Based on the density, which results glycerol via hydrolyzation of TAGs and loss of apoCs from VLDL to
from the percentage of the proteins and lipids in their structure, they transfer back to HDL. The VLDL is then converted to remnant VLDL or
are mainly divided into five major classes including HDL, LDL, IDL, IDL, which contains apoB-100 and apoE and is an interplayer between
VLDL and CMs [38]. The density of lipoproteins is associated with the VLDL and LDL [38]. The released energy components in the form of
percentage of their protein. In contrast, there is an inverse association glycerol and FAs are used by the skeletal muscles and adipocytes. As
between the size of a lipoprotein and its density. HDL is the smallest in CMs, the interaction of rVLDL or IDL with LDL receptors of the
lipoprotein and has more density with the highest percentage of liver in the presence of apoB-100 and apoE ends in TAG hydrolyzation
proteins (Figure 5). and loss of apoE to constitute the rIDL or LDL lipoproteins. ApoE is
Metabolism of lipoproteins and atherosclerosis transferred back to HDL. Therefore, the predominant apolipoprotein of
LDL is apoB-100. Lack of apoE in LDL decreases the affinity of LDL to
LDL poses pathological challenges relating to atherosclerotic its cognate receptors of the liver. Fusion of endosomes with lysosomes
plaque formation through the distribution of cholesterol from the liver leads to degradation of apolipoproteins and hydrolyzation of cholesterol
to the tissues and especially the endothelium [27]. Conversely, HDL is esters to free cholesterols, which is incorporated into the plasma
involved in the transport of lipids from tissues and back to the liver or membranes. Excess intracellular cholesterol enhances the activity of
excretion from the body, a process called reverse cholesterol transport acyl-CoA: cholesterol acyltransferase (ACAT) for re-esterification of
(RCT) [39]. Thus, HDL has an anti-atherogenic and protective effect cholesterol to the cholesterol esters for intracellular storage.
in the body. Chylomicrons and VLDL are involved in the transport
of TAGs. Chylomicrons transport the newly absorbed TAGs from the Many studies have shown that hypertriglyceridemia (with
intestine to the skeletal muscle for consumption, to the adipose tissue VLDL as TAG carrier) similar to hypercholesterolemia (with LDL as
for storage or to the liver for synthesis of VLDL. VLDL is secreted cholesterol transporter) is directly linked to the risk of cardiovascular
from the liver to the circulation for transport to other tissues including morbidity and mortality and atherosclerosis [48]. Atherosclerosis is an
adipose tissue. inflammatory disease that is triggered by oxidation of LDL cholesterol
(LDL-C), which in turn the oxidized LDLs (ox-LDLs) are trapped in
Another nomenclature, which is used for explanation of the the extracellular matrix of the sub-endothelial space [49]. The ox-LDL
lipoprotein metabolism pathway, based on the origin of their lipid, is is absorbed by the tissue macrophages to form foam cells (macrophages
exogenous and endogenous lipoprotein pathways. In the exogenous loaded with lipids) and promote inflammatory gene expression (e.g.,
lipoprotein pathway, the lipid components of the lipoproteins nuclear factor kappa-light-chain-enhancer of activated B cells (NF-
are synthesized by the intestine from dietary lipids, while in the kB) pathway) that initiate the inflammatory response. Inflammation
endogenous lipoprotein pathway the lipid components are synthesized primes the formation of fatty streak and in turn the arterial calcification
by the liver [40]. In the exogenous pathway, the intestinal lipids [50,51]. This is the starting point for the aggregation of coagulation cells
(TAGs, phospholipids, cholesterol) are absorbed by the epithelium that express different coagulation factors for initiation and maintenance
J Diabetes Metab
Page 9 of 19
HDL also, via extraction of the free cholesterol from cell membrane,
decreases the intracellular esterified cholesterol, which is mobilized
to the membrane to replace the membrane cholesterol. This process
happens via the action of ATP-binding cassette protein G1 (ABCG1).
HDL moves to the liver to bind the scavenger receptors class B type
I (SR-BI) and release its cholesterol esters to the hepatocytes through
caveolae; however, it is not absorbed to the hepatocytes.
HDL has a different effect on vascular biology. In normal state, the
apoA-I, GPx1, PON1 and PAF-AH of HDL have antioxidant properties;
whereas in the inflammatory state, these properties become inactivated
and HDL becomes proatherogenic. Besides, modification of apoA-I by
myeloperoxidase, which is produced from the atherosclerotic plaques,
tends to lower affinity of HDL for interaction with macrophage and
removal of cholesterol from foam cells.
HDL transfers its cholesterol esters to VLDL and LDL via the activity
of CETP and its RCT property. In this situation TAG is transferred
from VLDL to HDL. Ultimately, conversion of VLDL to LDL transfers
these cholesterol esters to the hepatocytes via LDL receptors. However,
some of the LDLs are oxidized in the peripheral tissues and induce
atherosclerosis. Furthermore, TAG-rich HDL is targeted by hepatic
lipase and becomes smaller and unstable and loses its apoA-I. In the
absence of apoA-I, HDL is not able to act as RCT. One approach for
increasing the circulatory level of HDL is inhibition of CETP. CETP
blockage reduces cholesterol transfer to VLDL and LDL and the level of
ox-LDL and also decreases the level of TAG-rich HDLs [55].
Lipoprotein Lipase (LPL)
These pancreatic, hepatic, and endothelial lipases are soluble
hydrolytic enzymes whose main function lies in the hydrolysis of TAGs
of the circulatory TAG-rich lipoprotein particles, namely CMs and
VLDL and converting their TAGs to non-esterified FAs (NEFA) and
Figure 6: Fatty acid beta-oxidation (FAO)
The cytoplasmic FAO reaction is a multistage process in which LCFAs are 2-monoacylglycerol [17,56,57]. They also increase the cellular uptake
degraded to the multiple two carbon glycolysis intermediate (acetyl-CoA) as well of rCM, cholesterol rich lipoproteins and FFAs. The apolipoproteins
as one three carbon component (propionyl-CoA) in the FAs that contain an odd of lipoprotein particles have a role in targeting of the lipoproteins to
number of carbon atoms. In this catabolic reaction, the reduced components
the tissues and also functions as a cofactor (especially apoC-II) for LPL
of the OXPHOS reaction (NADH2, FADH2) are produced. Abbreviations are
explained in figure 2. although apoC-III is an inhibitor of LPL activity [58,59]. Apart from its
enzymatic function, LPL has an important role in lipid metabolism and
transport. LPL also acts simultaneously as a linker between lipoproteins
of a coagulation state for a short period and tissue repair that is followed and cell surface receptors, including proteoglycans such as cell surface
by stimulation of the fibrinolysis pathway for ending and removing this related LDL receptors and heparan sulfate proteoglycans (HSPG) and
process [52]. ApoD via its influence on lipid metabolism affects the thus facilitates the uptake of lipoproteins by the tissues [59]. In the
process of atherosclerosis and ageing [53,54]. literature, malfunctioning of LPL has been associated with a plethora
HDL with its anti-inflammatory, antioxidant and vasodilatory of pathological conditions including atherosclerosis, obesity, diabetes,
properties is considered as the atheroprotective particle. These chylomicronemia, Alzheimer disease, and cachexia [60,61].
effects are produced as a result of the role of HDL in RCT. HDL Expression of LPL is mediated through a complex interaction
is synthesized in the liver and small intestine with the property between sterol regulatory element-binding protein (SREBP),
that it is devoid of any cholesterol and cholesteryl esters and cytokines, LPS [60], peroxisome proliferator-activated receptor-alpha
contains apoA-I, apoC-I, apoC-II and apoE and enzymes including (PPAR), cyclic adenosine 3,5-monophosphate (cAMP) response
glutathione peroxidase-1 (GPx1), paraoxonase-1 (PON1), platelet element binding protein (CREBP) and activator protein-1-like
activating factor acetylhydrolase (PAF-AH, also called lipoprotein- factors [60,62,63]. In addition, expression of LPL is enhanced by the
associated phospholipase A2, Lp-PLA2), lecithin: cholesterol differentiation of macrophage and adipocyte and is under the influence
acyltransferase (LCAT), cholesterol ester transfer protein (CETP) and of specific nutritional factors, blood glucose levels, FAs, and the levels
sphingosine-1-phosphate (S1P). GPx1, PON1 and PAF-AH have of hormones such as insulin, catecholamine, thyroid hormones, growth
antioxidant activities. HDLs, via apoA-I and the action of ATP binding
hormone, estrogen, prolactin, parathyroid hormone, retinoic acid and
cassette transporter A1 (ABCA1), interact with macrophages in the
vitamin D3 [60]. LPL is produced in the parenchymal cells of adipocytes,
subendothelial space of the tissues to transfer cholesterol from the
heart, skeletal muscles as well as macrophages and is distributed along
macrophages and form pre- HDL. The free cholesterol, through
the vascular mesh [60]. Thereafter, it is secreted and translocated to the
interaction with apoA-I, is then esterified by LCAT and internalized
functional heparan sulphate proteoglycan (HSPG)-binding site on the
into the hydrophobic core of the pre- HDL particle and enlarged to
luminal surface of the endothelium and hydrolyzes lipoproteins [64].
HDL2 and HDL3.
J Diabetes Metab
Page 10 of 19
The level of LPL production in adipose tissue and the skeletal

muscle determines whether dietary lipids are mainly stored in the
adipose tissue (to induce obesity) or are used for energy consumption
in the skeletal muscle (to induce weight loss). Thus, the control of LPL
production is important for understanding obesity and pathological
weight loss [65,66]. During fed state, the activity of enzymes is more
in the adipose tissue than the skeletal muscle to store the extra energy,
while exercise leads to a higher level of enzyme activity in the skeletal
muscle [45,67]. Therefore, expression of LPL by adipose tissue and
skeletal muscle is often considered to constitute an anti-atherogenic
influence, while the expression of LPL by the endothelial cells and
macrophages has a pro-atherogenic effect. In this way, import of LDL
to macrophages and foam cell formation in the subendothelial space
is the main trigger of atherosclerosis pathogenesis. Insulin is the main
regulator of the LPL activity in adipose tissue. During fed state, insulin
upregulates LPL expression and consequently FA storage in adipose
tissue. However, in fasting state, the level of insulin is low and LPL
expression is increased in the skeletal muscle that leads to absorption
of fats by the skeletal muscles. Moreover, insulin unresponsiveness is
associated with a proinflammatory state of adipose tissue in which
production of cytokines such as Tumor necrosis factors alpha (TNF)
and interleukin 6 (IL-6) reduces LPL expression in adipose tissue [45].
This leads to hypertriglyceridaemia and susceptibility to coronary
artery disease. Cytokine-induced inhibition of LPL expression in
adipose tissue is also the pathophysiology of cachexia in cancers [67].
Thus, it is expected that anti-geriatric factors, if they exist, should also
influence LPL activity.
Fatty Acid beta-Oxidation (FAO)
FAO is a mitochondrial (and peroxisomal for LCFAs) process in
which the conserved energy of the FAs is released in a stepwise manner.
FAs are long carbon chain molecules that during FAO and in each
step, 2 carbon molecules of FA are degraded to produce the activated
2-carbone (2c-) intermediate, acetyl-CoA. In addition, reduction of Figure 7: Fatty acid synthesis
This cytoplasmic anabolic reaction happens when the concentration of acetyl-
NADH+ and FADH+ cofactors produces NADH2 and FADH2 during CoA (the intermediate of glucose degradation pathway) is high. This means
FAO. Degradation of FAs with odd number of carbons (produced that in high consumption of carbohydrates and excess amount of energy in the
in some bacteria) produces one molecule propionyl-CoA and one body, some part of acetyl-CoA is converted to FAs for storage in the form of
TAG. Insulin, that is the main hormone of pancreatic beta cells and is released
molecule acetyl-CoA instead of two molecules acetyl-CoA in the last
during feeding state, stimulates this process. NADPH2 cofactor (product of
step. Propionyl-CoA converts to methylmalonyl-CoA and succinyl- the pentose phosphate pathway) is required in this process. Abbreviations are
CoA to enter the Krebs cycle (Figure 6). explained in figure 2.
Oxidation of FAs happens in two stages in the cytoplasm and in

the mitochondria. In the cytoplasmic stage, FAs are first activated dehydrogenase and NAD+ coenzyme to produce beta ketoacyl-CoA.
via conversion to acyl-CoA by using fatty acyl-CoA synthase (or Beta ketoacyl-CoA is degraded to acetyl-CoA and acyl-CoA molecule
thiokinase), Mg2+ as cofactor, coenzyme A (CoA-SH) and ATP. with 2 carbons less than the first acyl-CoA molecule by using beta-
Thereafter, acyl-CoA, by using acyl-carnitine palmitoyltransferase ketothiolase (or acetyl-CoA acyl transferase) and one molecule CoA-
transferase I (CPT-I), forms a complex with carnitine (or beta- SH. This acyl-CoA is dehydrogenated again to start the second cycle
hydroxy-gamma-trimethylammonium butyrate) in order to pass of the process to lose two extra carbons. This process continues till the
the mitochondrial membrane. Carnitine is produced from the lysine long chain of FA becomes completely degraded to acetyl-CoA [68].
amino acid in the liver and kidney cells. Therefore, any problem in the Energy balance in FAO
metabolism of lysine leads to disturbance in the formation of carnitine
and consequently FA metabolism and storage of TAGs in cells. In acyl- In the Krebs cycle, degradation of each acetyl-CoA produces 12
CoA with long chain hydrocarbons, acylcarnitine translocase enzyme ATP molecules. Each propionyl-CoA produces 6 ATP that is yielded
transfers the acylcarnitine across the IMM. from 1 GTP, 1 FADH2 (equal to 2 ATP) and 1 NADH2 (equal to 3 ATP).
Furthermore, conversion of propionyl-CoA to succinyl-CoA requires
In the mitochondrial stage, acyl-CoA via acyl-carnitine transferase 1 ATP. Therefore, each propionyl-CoA at the end produces 5 ATP. In
II, becomes separated from acyl-carnitine. Subsequently, acyl-CoA addition, in each cycle of beta oxidation, which leads to degradation
becomes dehydrogenated by using acyl-CoA dehydrogenase (a of one acetyl-CoA from the LCFAs, 1 FADH2 and 1 NADH2 are
flavoprotein) and flavin adenine dinucleotide (FAD) coenzyme to produced. The number of cycles for each molecule of FA is calculated
produce dehydroacy-CoA (or enoyl-CoA). Dehydroacyl-CoA becomes by subtracting one from the number of the final products. Moreover,
hydroxylated by using hydratase and one molecule water to produce at the level of thiokinase reaction 1 ATP is consumed that should be
beta-hydroxyacyl-CoA. This product becomes oxidized by using considered in the final calculation.
J Diabetes Metab
Page 11 of 19
Examples First stage: Each 17C-FA produces 7 2C-acetyl-CoA, which is

equal to 84 ATP as well as one 3C-propionyl-CoA that produce 5 ATP.
1. How many ATP molecules are produced from a 6-carbon FA?
Second stage: Total number of cycles that is used for total
First stage: Calculation of the number of products (including degradation of 17C-FA is 7. This amount is calculated by consideration
2C-acetyl-CoA and 3C-propionyl-CoA) that is yielded from each of the total number of products (8 molecules in this example) minus
molecule of 6C-FA. Each 6C-FA produces 3 2C-acetyl-CoA molecules, one. The total amount of energy production in each cycle is equal to
which produces 36 ATP. 35 ATP.
Second stage: Calculation of the number of cycles that is used for Third stage: Consideration of the consumption of one ATP by
complete degradation of 6C-FA. The total number of cycles is equal to thiokinase
the total number of products (acetyl-CoA in the odd-numbered FAs)
that is yielded at the end of the degradation (3 acetyl-CoA in this Final calculation: 84 ATP + 5 ATP + 35 ATP - 1 ATP = 123 ATP
example) minus one. As in each cycle 5 ATP is produced, via OXPHOS
reaction of 1 NADH2 and 1 FADH2, therefore, during degradation of
Regulation of FAO
each 6C-FA totally 10 ATP are produced in two cycles. The level of acetyl-CoA is one of the main determinant parameters
in the regulation of FAO. Acetyl-CoA is the product of glucose
Third stage: Consideration of the consumption of one ATP by
degradation during glycolysis and pyruvate dehydrogenase (PDH)
thiokinase.
reaction as well as FAO. Therefore, acetyl-CoA is the main linker
This amount is used just one time; therefore, it should be considered molecule between the carbohydrate and lipid pathways. Acetyl-CoA
at the end of the calculation. is consumed in different pathways including (i) the Krebs cycle, (ii)
gluconeogenesis using pyruvate carboxylase (PC), (iii) oxaloacetate
Final calculation: 36 ATP + 10 ATP - 1 ATP = 45 ATP
production by using CO2 to store glucose in the liver as glycogen, (iv) FA
2. How many ATP molecules are produced from a 17-carbon biosynthesis and (v) cholesterol synthesis [69]. One of the parameters
FA? that influence the concentration of acetyl-CoA in the body is hormones.
In physiological states, insulin is secreted from the pancreatic beta cells
following feeding. Insulin is an antilipolytic hormone and the inhibitor
of FAO [70]. This means that in excess of energy level in the body
carbohydrate catabolism proceeds to lipid storage. In diabetic states,
insulin unresponsiveness decreases the level of lipogenesis. This leads
to lipolysis and elevation of the level of FFAs in circulation. FFAs are
sedimented to non-adipose tissues such as skeletal muscle and liver to
enhance FAID in these organs [14]. In type 1 diabetic state and shortage
of insulin, FAO and acetyl-CoA production in the body is increased.
Acetyl-CoA is the substrate of 3-hydroxy-3-methyl-glutaryl-CoA
(HMG-CoA), which is the substrate of HMG-CoA lyase in the ketone
bodies pathway.
Fatty Acid Synthesis

FA synthesis starts when the concentration of acetyl-CoA in
cytoplasm is high. This cytoplasmic process happens via the enzymatic
activity of a single, homodimeric, multifunctional protein, the FA
synthase (FAS) complex. Each FAS monomer contains three catalytic
N-terminal domains including beta-ketoacyl-ACP synthase (KS),
malonyl/acetyl transferase (MAT) and dehydrase (DH) and four
C-terminal domains including enoyl-ACP reductase (ER), beta-
ketoacyl-ACP reductase (KR), (ACP) and thiosterase (TE) that are
separated from each other by a structural core. The conserved ACP
(central protein) acts as the mobile domain responsible for shuttling the
intermediate fatty acid substrates to various catalytic sites. Coenzyme
A is the source of the phosphopantetheine prosthetic group of the
ACP domain, which contains thiol (central SH). One of the peripheral
enzymes (KS) also contains thiol (peripheral SH), which belongs to the
cysteine amino acid [71].
During FA synthesis, acetyl-CoA is carboxylated to malonyl-
CoA in cytosol by using acetyl-CoA carboxylase (ACC), ATP, CO2
and biotin as coenzyme. Thereafter, malonyl transacylase and acetyl
Figure 8: Fatty acid synthase (FAS)
transacylase separate CoA-SH from malonyl-CoA and acetyl-CoA
Elongation of the fatty acids happens on the FAS complex, which contains a
central protein (ACP) and peripheral enzymes around this protein. Junction roots and join malonyl roots to the ACP domain (central SH) and acetyl
of the new acyls to the complex always happens in the central protein. After roots to the active site of cysteine thiol of the KS domain (peripheral
four stages, the elongated acyl transfers from central protein to the peripheral SH). Subsequently, one molecule CO2 is released from the malonyl
protein to release the central protein for adhesion of new malonyl-CoA to FAS.
root using carboxylase and the acetyl root joins to the rest of the
J Diabetes Metab
Page 12 of 19
molecule on the central SH to produce acetoacyl-ACP. Acetoacyl-ACP

becomes reduced using reductase and NADH2 phosphate (NADPH2)
as coenzyme and produces -hydroxyacyl-ACP. Thereafter, dehydrase
separates one H2O to produce -dehydroacyl-ACP (or enoyl-ACP),
which is reduced by using -dehydroacyl-ACP reductase and NADPH2
to produce butyryl-ACP (4C-acyl-ACP). Consequently, the butyryl
root is again transferred from the central thiol to the peripheral thiol
and the central thiol becomes free again for joining to a new malonyl
root (Figure 7,8).
The final product of this cycle is palmitoyl-ACP. Palmitoyl-ACP is
released from the enzymatic complex using deacylase and one molecule
water to produce palmitate, which is a 16C-FA. Mitochondria and
microsomes produce FAs with longer chains or with unsaturated bonds
[72,73]. Insulin is a lipogenic hormone that stimulates synthesis of both
the FAs and cholesterol with the regulation of SREBP-1c and SREBP-2
in each pathway respectively [74].
Regulation of fatty acid synthesis
ACC is the main regulatory enzyme of FA synthesis that is regulated
in three different ways including (i) allosteric reaction of the local
metabolites, (ii) hormones and (iii) phosphorylation. Allosterically,
palmitoyl-CoA, a LCFA, is the inhibitor and citric acid is the stimulator
of ACC [75]. Excess of acetyl-CoA, through stimulation of the Krebs
cycle and citrate synthesis, is converted to malonyl-CoA and stored as
FAs [76]. Malonyl-CoA inhibits transport of FAs to the mitochondria
for FAO [77]. Phosphorylation of ACC by 5 AMP-activated protein
kinase (AMPK) decreases the level of malonyl-CoA and inhibits FA
synthesis [76]. AMPK is activated when the intracellular energy is
low. AMPK also stimulates FAO by augmenting the inhibitory effect Figure 9: Triacylglycerol (TAG) biosynthesis
of malonyl-CoA for transport of FA to the mitochondria. In low level Esterification of glycerol with three FAs produces TAG. This anabolic
of glucose (e.g., in type 1 diabetes), stimulation of cAMP/PKA (protein cytoplasmic pathway mostly happens in the liver and AT. Liver TAGs are
transferred to adipose tissue using VLDL and the TAGs of adipose tissue
kinase A) pathway by glucagon and epinephrine [78] inhibits AMPK; is reserved in the adipocytes- LDs to be used at the time of starvation.
therefore, acetyl-CoA is consumed in ketogenesis pathway instead of Abbreviations are explained in figure 2.
FA synthesis [79]. Ketone bodies are the other energy source of the
body in situations in which the level of glucose in the body is low. In
phosphatidic acid. Phosphatidic acid, using phosphatase, loses one
high glucose level, insulin stimulates the pentose phosphate pathway
phosphate group and produces DAG. DAG, using TAG synthase,
[80] as well as ACC and FA synthesis [81]. Upstream regulatory factors
combines with one extra acyl-CoA and produces TAG (Figure 9). TAG
(USFs) and SREBP-1 transcription factors mediate this process [82].
is then transported to VLDL of the liver as well as the adipocytes-LDs
Polyunsaturated FA in the liver [83] and leptin in adipocyte inhibit
[85]. Glycerol can also follow gluconeogenesis to produce glucose and
expression of SREBP [84].
glycogen [69].
Triacylglyceride (TAG) Synthesis TAG Degradation
Esterification of three FA molecules with glycerol produces TAGs. TAGs are sequentially hydrolyzed by the activity of desnutrin/
TAGs are the main lipid components of LDs and are stored in adipose ATGL, hormone-sensitive lipase (HSL) and MAG lipase (MAGL)
tissues, skeletal muscles, liver, lungs and intestine to provide energy for to produce FAs and glycerol [86-88]. The liberated FAs are used in
the metabolic processes. In adipose tissue, there is a balance between different ways including (i) as the source of energy at the time of energy
degradation and synthesis of fats in normal state. deprivation, (ii) for re-esterification in AT, (iii) for beta oxidation in
The first step of TAG synthesis is consumption of glycerol in the other tissues and (iv) for storage as phospholipids or other lipid types.
form of glycerol-3-phosphate (G3P). G3P is produced in two different Dysregulation of hormones such as insulin and androgens during
ways in the liver and adipose tissue. In the liver, G3P is made by stress (e.g., fasting) or metabolic system disorders such as obesity-
phosphorylation of glycerol using glycerol kinase and ATP. Glycerol is induced metabolic syndrome and lipodystrophy affects the function
derived from degradation of adipocyte-TAGs and is transferred to the of lipolytic enzymes in adipose tissue. Under fasting state, the level of
liver via circulation. In adipose tissue, synthesis of G3P via the liver the catecholamines increases in adipose tissue due to absorption by
circulation or by sympathetic innervations. Catecholamines increase
pathway does not happen due to the lack of glycerokinase; however,
the adenylate cyclase activity and intracellular cAMP concentration
G3P is made from reduction of dihydroxyacetone phosphate (DHAP,
and PKA activity and consequently phosphorylation and stimulation
glycolysis metabolites) by glycerol-3-phosphate dehydrogenase
of hydrolytic activity of HSL, which is translocated to the adipocytes-
(G3PDH).
LDs for TAG breakdown. Glucocorticoids, via stimulation of the
In the next step, two molecules of acyl-CoA (FAs) join to G3P desnutrin/ATGL enzymes, can also stimulate lipolysis [87]. In fed state,
using phosphatidic synthetase or fatty-acyl-CoA transferase to make insulin inhibits lipolysis by dephosphorylation of HSL and activation
J Diabetes Metab
Page 13 of 19
regulation of TAG is lipin-1. It also has an effect on mitochondrial

oxidation, development of mature adipocytes, storage and utilization
of glucose and FAs of peripheral tissues [100,101]. They interact
with some gluconeogenic nuclear receptors such as PPAR-gamma
coactivator-1-alpha (PGC-1), PPAR, glucocorticoid receptor (GR)
and hepatocyte nuclear factor-4-alpha (HNF4) [102]. During the
acute phase of inflammation, LPS and proinflammatory cytokines
negatively regulate lipin1 in adipose tissue and therefore the level of
FFAs and VLDL is increased in circulation [101]. Both adrenaline and
contraction-mediated events mediate TAG hydrolysis by HSL [103].
These events deactivate AMPK secretion and activate PKC/ERK and
Figure 10: Ketone bodies synthesis

Ketone bodies are the product of HMG-CoA, which is produced from assembly
of three acetyl-CoA. During type 1 diabetes, shortage of insulin production
by pancreatic beta cells stimulates intracellular FAO and the concentration of
acetyl-CoA, which is used for Ketone bodies production. Ketone bodies are
one of the energy sources of cells. Abbreviations are explained in figure 2.
of phosphodiesterase (PDE) that decreases the level of cAMP. Insulin,

via phosphoinositide-3-kinase/AKT (PI3K/AKT (also known as PKB))
pathway, phosphorylates and inhibits PDE3B which has an inhibitory
effect on the cAMP activity. Another inhibitory effect of insulin on
lipolysis is through phosphoprotein phosphatase-1 (PP1) and its
negative regulation on HSL [87].
Other pathways for phosphorylation of HSL are via 3,5- cyclic
guanosine monophosphate (cGMP) dependent kinase [89] and
calcium-induced protein kinase C/ mitogen-activated protein kinases
/ extracellular-signal-regulated kinase (PKC/MAPK/ERK) activity
[90,91] that activate HSL. AMPK inactivates HSL lipolytic property
and has a competitive effect with PKA in HSL phosphorylation and
activity [17,92]. Another regulator of HSL activity is perilipin A that
associates with LD and enhances HSL lipolytic activity [92,93]. In basal
states, perilipin A maintains a low rate of lipolysis in the LDs; however,
under hormone stimulation, PKA-mediated perilipin phosphorylation
through facilitating the HSL translocation to the LDs or its interaction
with HSL, stimulates HSL activity. HSL has an effect on broad substrates
of lipid molecules including TAG, DAG, MAG, retinyl and cholesteryl
esters, but it mostly affects DAG and cholesteryl ester [94].
Desnutrin/ATGL contains a patatin-like domain that hydrolyzes
TAG and does not hydrolyze cholesteryl and retinyl esters [86].
Desnutrin expression is limited to adipose tissue and is overexpressed
in adipocyte differentiation and glucocorticoid stimulation and is
downregulated during feeding and insulin stimulation [88]. Other
parameters that are important in lipolysis are thyroid hormone, growth
hormones [95], natriuretic peptide, alpha-melanocyte stimulating
hormone (-MSH) and TNF that stimulate lipolysis [96,97]. Adenosine
[98] and neuropeptide Y [99] inhibit lipolysis while prostaglandins
such as PGE2 and PGI2 have a bipolar effect.
Figure 11: Cholesterol synthesis
Excess amount of energy (or high concentration of acetyl-CoA) in cell is stored
Regulation of Triglyceride Metabolism as lipid. Cholesterol synthesis happens in the cytoplasm of liver and adipose
tissue following consumption of ATP and NADPH2. Abbreviations are explained
Insulin has an antilipolytic effect and beta-adrenergic hormones in figure 2.
have a stimulatory effect on TAG degradation. Another protein for
J Diabetes Metab
Page 14 of 19
cAMP/PKA pathways that are activated by muscle contraction-induced acid-CoA combines with one CoA-SH and produces two acetyl-CoA
intracellular calcium release and epinephrine stimulation that lead to using beta ketothiolase. In skeletal muscles, the first stage of ketone
PKC and ERK activation and stimulation of HSL [17,104]. bodies degradation occurs in different ways. In skeletal muscles,
succinyl-CoA (instead of ATP) is used for combination of CoA-SH
Adenylyl cyclase has an important role in lipid metabolism.
to acetoacetic acid; therefore, totally 23 ATP are produced in skeletal
Adenylyl cyclase, via conversion to ATP to cAMP, activates protein
muscles, while this amount in other cells is 24 ATP. Degradation of
kinase using one ATP molecule. Activated PKA phosphorylates and
acetoacetyl-CoA to two acetyl-CoA produces 24 ATP because each
activates TAG lipase [104]. Glycerol and FA, which are produced from
acetyl-CoA produces 12 ATP during the Krebs cycle.
TAG, are transferred to the liver via circulation.
Hormones through influence on adenylyl cyclase are able to Regulation of ketone body synthesis
regulate lipid metabolism. Epinephrine (adrenaline), norepinephrine During fasting, TAG-adipocyte is degraded to release its energy.
(noradrenaline) [105], glucagon [106,107], adrenocorticotropic Over-supply of TAG in the liver induces synthesis of ketone bodies.
hormone (ACTH) [108], hydrocortisone [109], thyroxine [110], This event happens when the insulin / glucagon ratio is decreased in
serotonin [111] and thyroid-stimulating hormone (TSH) [112] directly fasting state. Therefore, in high level of glucagon, ACC is inhibited and
influence adipocytes and stimulate adenylyl cyclase and lipolysis consequently FAO is stimulated. In FAO, fatty acyl-CoA is converted to
[113]. Conversely, insulin has a negative regulatory effect on adenylyl acetyl-CoA to be used in the Krebs cycle for energy production. In this
cyclase and hence inhibits lipolysis. Therefore, insulin is an antilipolytic state, NADH2 / NAD+ ratio increases. In high level of this ratio and when
or lipogenesis agent; however, the antilipolytic effect of insulin is enough energy supply of the hepatocytes is prepared, the extra acetyl-
independent of this effect [114]. Insulin functions in different ways CoA is consumed in the ketogenesis pathway. Moreover, oxaloacetate
to inhibit lipolysis including (i)activation of PDE, which catalyzes is converted to malate to generate glucose via gluconeogenesis. In the
the conversion of cAMP to 5/ AMP [115]. (ii) stimulation of entrance chronic fasting state, gene expression of mitochondrial HMG-CoA
of glucose to cells and glycolysis that increases DHAP concentration synthase is stimulated that induces the ketogenesis pathway.
(substrate of FA synthesis), (iii) activation of FAS (enzyme of FA
synthesis), (iv) inhibition of TAG degradation via inhibition of HSL, Cholesterol Biosynthesis
(v) activation of glycogen synthase to convert G3P to glycogen and
(vi) activation of glucose-6-phosphate (G6P) dehydrogenase (G6PDH) Cholesterol is one of the main fat components of the body that has
that stimulates the pentose phosphate pathway and produces NADPH2 both external (foods like egg, meat and milk) and internal sources.
(cofactor for FA synthesis). In this stage also the concentration of DHAP Inside the body cholesterol is made from acetyl-CoA in hepatocytes,
increases and is reduced via G3PDH and produces G3P (substrates of enterocytes, testes and ovaries [117] and contains less than 60% of the
TAG synthesis). total proportion of cholesterol in the blood. Acetyl-CoA is yielded from
oxidation of glucose and FAs.
Ketone Bodies In the cytoplasmic process of cholesterol biosynthesis 3 acetyl-CoA
Ketone bodies are acetone (C-CO-C), acetoacetic acid (C-CO- are joined to each other to produce HMG-CoA. HMG-CoA can either
C-COOH) and beta hydroxyl butyric acid (C-C(OH)-C-COOH). follow cholesterol production by the function of HMG-CoA reductase
Normally, the concentration of these products in the circulation is or enter the ketogenesis pathway. NADPH2 is the cofactor of this process
low (1 mg/dl); however, in type 1 diabetes, anesthesia and prolonged that is produced from the pentose phosphate pathway (Figure 11).
fasting their concentration increases and leads to ketosis and metabolic
acidosis. When the concentration of ketone bodies in the serum
Regulation of cholesterol synthesis
exceeds the threshold absorption by the kidney tubules, it is released Cholesterol synthesis is regulated through the enzymes of this
in the urine (ketonuria). In normal states, the concentration of ketone pathway. These are 3-hydroxy-3-methyl-glutaryl-CoA reductase
bodies is not detectable in the urine. Ketone bodies are produced in (HMG-CoAR) and acyl-CoA: cholesterol acyltransferase (ACAT),
the liver, testes and ovaries [116], and are transported to the brain and for regulation of intracellular free cholesterol as well as LDL receptor-
cardiac muscles for consumption as energy source via conversion to mediated uptake and HDL-mediated reverse transport that regulate
acetyl-CoA (Figure 10). the plasma cholesterol level. HMG-CoAR is the rate limiting and
key sterol synthetic enzyme that has 8 transmembrane (8TM) spans
Synthesis of ketone bodies
and is anchored to the ER membrane. It is regulated by the level of
In this cytoplasmic reaction, two acetyl-CoA produce acetoacetyl- cellular cholesterol. High level of cholesterol has a negative feedback
CoA using beta-ketothiolase. Acetoacetyl-CoA produces HMG-CoA effect on HMG-CoAR and its gene expression. In addition, cholesterol
using HMG-CoA synthase and acetyl-CoA. HMG-CoA loses one stimulates HMG-CoAR polyubiquitination and degradation which is
acetyl-CoA using HMG-CoA lyase and produces acetoacetic acid, modulated by its transmembrane (TM) sterol-sensing domain (SSD)
which follows two pathways; it becomes reduced and produces beta and its role in proteasome degradation. HMG-CoAR is also regulated
hydroxyl butyric acid using beta hydroxyl butyric acid dehydrogenase by phosphorylation and dephosphorylation. Phosphorylation of HMG-
and NAD+ or it loses one CO2 and produces ketone using acetoacetate CoAR inhibits its function. HMG-CoAR phosphorylation happens
decarboxylase. either via activated AMPK [118] or activated protein phosphatase
inhibitor-1 (PPI-1). The phosphorylated forms of AMPK and PPI-
Degradation of ketone bodies 1 are active. Activated PPI-1 inhibits HMG-CoAR phosphatase
In order to use ketone bodies as energy source, the body only uses (also called PP2A), which dephosphorylates (and activates) HMG-
acetoacetic acid. Acetone evaporates quickly and is discharged via CoAR. Activated PPI-1 also inhibits PP2C, which dephosphorylates
ventilation and hydroxyl butyric acid is converted to acetoacetic acid. (and inactivates) AMPK. Inactivated HMG-CoAR phosphatase and
During degradation, acetoacetic acid is converted to acetoacetic acid- phosphorylated AMPK maintain HMG-CoAR in the phosphorylated
CoA via thiokinase and using CoA-SH and ATP. Thereafter, acetoacetic (and inactivated) states [119]. Glucagon and epinephrine decrease
J Diabetes Metab
Page 15 of 19
cholesterol synthesis through activation of the PPI-1 inhibitor, while Subsequently, two separate site-specific proteolytic cleavages by S1P and
insulin dephosphorylates (and activates) HMG-CoAR [120]. S2P proteins happen that release the membrane-bound SREBP to the
cytoplasm. The released SREBP2 translocates to the nucleus to function
SREBP is the master regulator of lipid homeostasis [121] and a
as transcription factor for upregulation of cholesterol synthesis genes
transcription factor that enhances lipogenesis in adipose tissue by
including HMG-CoAR. After a short period, SREBP is ubiquitinated
controlling the gene expression of enzymes of lipid synthesis. These
and degraded to become inactive (Figure 12) [123].
genes are cholesterol synthesis enzymes (HMG-CoA synthase, HMG-
CoA reductase, farnesyl diphosphate synthase and squalene synthase), Conclusion
FA synthesis enzymes (ACC, FAS, stearoyl-CoA desaturase (SCD)) and
TAG synthesis enzyme (G3P acyltransferase (GPAT)) and also for lipid Lipid-carbohydrate interaction is one of the fundamental
uptake (e.g., LDL receptor) [122]. The concentration of cholesterol parameters in regulation of the energy metabolic system. Disturbance
in ER determines the regulation of gene expression in cholesterol in the function of the adipose tissue as the main fat storage organ of
synthesis. The synthetic sterol, through a negative feedback loop, the body leads to FAID and consequently metabolic disorders. In this
inhibits the cleavage of SREBP and synthesis of additional sterol review, the biochemical pathways of the main energetic molecule of
the body (lipids) are summarized in such a way that researchers can
SREBP is in three isoforms of SREBP-1a (involved in both the follow the association between these pathways easily. Understanding
FA and cholesterol synthesis), SREBP-1c (involved in FA synthesis) these biochemical pathways will help biologists to comprehend the
and SREBP-2 (involved in cholesterol synthesis and LDL receptor pathophysiology of metabolic diseases properly.
gene expression). The inactive precursor of SREBP is bound to the
ER membrane. The three TM proteins of ER membrane (SREBP2, Nomenclatures
SREBP cleavage activating protein (SCAP) and Insig) and the two
Acetyl group, (also named methyloxidocarbon or ethanoyl group)
cleavage proteins (site-1 protease (S1P) and site-2 protease (S2P))
is the organic group of acetic acid (C-CO-OH). Acetyl group is the acyl
regulate formation of SREBP. SREBP precursor protein is a 2TM-
with the chemical formula C-CO-. The acetyl group contains a methyl
protein that belongs to the basic helixloophelix (bHLH)-Zip family
group single bonded to a carbonyl. The acetyl moiety is a component
of transcription factors and contains one cytosolic C terminal SCAP
of many organic compounds such as acetyl-CoA, acetylcysteine,
binding domain and one cytosolic N terminal SREBP domain that
acetylcholine, acetaminophen (or paracetamol) and acetylsalicylic acid
mediates the dimerization, nuclear entry and DNA binding to sterol
regulatory element (SRE) segment to enhance the genes encoding (or aspirin).
for biosynthesis of lipids. The cholesterol-sensing protein, (SCAP), is Acyl group is an alkyl group attached to a carbon-oxygen double
an 8TM-protein containing SSD domain similar to HMG-CoAR. Its bond (R-CO-). Acylation is the substitution of an acyl group into
cytosolic domain binds to the cytosolic C terminal domain of SREBP something. The simplest acyl group is ethanoyl group (C-CO-).
protein. High level of sterol forms a complex with 6TM-Insig and SCAP Ethanoyl chloride is made by joining a chloride atom with an ethanoyl
and induces binding of the SSD of SCAP with the Insig protein. The group (C-CO-Cl).
Insig protein which always stays in the ER membrane, retentes SREBP-
SCAP precursor complex in the ER and inactivates it. Aldehyde is an organic compound with the structure R-CHO
consisting of a carbonyl center (CO) bonded to hydrogen and an R
In low concentration of sterol, the complex does not interact with the group, which is any generic alkyl or side chain. In aldehydes, carbonyl
Insig protein. Conformational change in SCAP leads to SREBP-SCAP is located at the end of a carbon skeleton, while in ketones carbonyl is
complex translocation to the Golgi apparatus using COPll vesicles. placed between two carbon atoms.
Aldehyde group or formyl group is the aldehyde group without R
(-CHO).
Aliphatic molecules are basically non-cyclic or cyclic molecules
that are not aromatic. Thus, instead of the normal benzene ring that has
3 double bonds inside, it is just a saturated closed ring.
Amphipathic molecules are molecules that contain both polar
(hydrophilic) and non-polar (hydrophobic) regions.
Alkane is an acyclic structure of saturated hydrocarbon that
consists of only hydrogen and carbon that join together with single
bonds. Their general chemical formula is CnH2n+2. Each carbon atom is
able to bind to four hydrogen or carbon atoms and each hydrogen atom
can join to one carbon atom. Carbon skeleton or carbon backbone is a
series of linked carbon atoms that are joined together. The size of the
alkane depends on the number of carbons that makes the molecule. The
Figure 12: Illustration of the role of SREBP in lipid production induction simplest alkane is methane (CH4).
In high concentration of sterol in the cytoplasm, SREBP transcription factor is
in an inactive form as it makes a complex with SCAP and together anchor to Alkoxy group is an alkyl group singular bonded to oxygen (R-O).
Insig protein of ER membrane. In depletion of sterol this anchored junction is
released and the SREBP-SCAP complex is transferred to the Golgi apparatus.
The simplest alkoxy groups are methoxy (R-O-C) and ethoxy group
SREBP is cleaved by 2 proteases (S1P and S2P). Degradation of SREBP (by (R-O-C-C).
S1P) and release of its bHLH domain (by S2P) and its transfer to the nucleus
induces the process of lipid production. Abbreviations are explained in figure 2. Alkyl is an alkane missing one hydrogen atom. An acyclic alkyl has
the general formula CnH2n+1. The smallest alkyl group is methyl Methyl
J Diabetes Metab
Page 16 of 19
group is a hydrocarbon and an alkyl derived from methane, containing Acknowledgement

one carbon atom bonded to three hydrogen atoms (-CH3). An alkyl I would like to express my ultimate appreciation to Dr. Nessa Dashty
group is symbolically abbreviated with R. A cycloalkyl is generated by Rahmatabady for her useful comments in this paper.
removal of a hydrogen atom from a cycloalkane and formation of a ring
References
with the general formula CnH2n-1.
1. Robert Robert Kincaid Murray (2000) Harpers biochemistry, Appleton & Lange,
Aryl group is the substituent derived from an aromatic ring, ISBN: 0838536840, 9780838536841.
including phenyl, naphthyl, thienyl, indolyl, etc. A simple aryl group is 2. Boelsma E, Hendriks HF, Roza L (2001) Nutritional skin care: health effects of
phenyl, C6H5, which is derived from benzene. micronutrients and fatty acids. Am J Clin Nutr 73: 853-864.
Aryloxy groups have an aryl group singular bonded to oxygen 3. Neyrolles O, Hernndez-Pando R, Pietri-Rouxel F, Forns P, Tailleux L, et al.
(2006) Is adipose tissue a place for Mycobacterium tuberculosis persistence?
(R-O-aryl). An alkoxy or aryloxy group bonded to an alkyl or aryl (R1- PLoS One 1: e43.
O-R2) is ether. If bonded to H it is an alcohol. An alkoxide (RO) is the
ionic or salt form; that is a derivative of an alcohol where the proton has 4. Lev S (2012) Nonvesicular lipid transfer from the endoplasmic reticulum. Cold
Spring Harb Perspect Biol 4.
been replaced by a metal, typically sodium.
5. Soccio RE, Breslow JL (2004) Intracellular cholesterol transport. Arterioscler
Carbonyl group is a functional group composed of a carbon atom Thromb Vasc Biol 24: 1150-1160.
double-bonded to an oxygen atom (C=O). This structure is found in 6. Dou M, Ma AG, Wang QZ, Liang H, Li Y, et al. (2009) Supplementation with
different compounds including aldehyde (R-CO-H), ketone (R1-CO- magnesium and vitamin E were more effective than magnesium alone to
R2), carboxylic acid (R-CO-OH), ester (R1-CO-OR2), amide (R1-CO- decrease plasma lipids and blood viscosity in diabetic rats. Nutr Res 29: 519-
524.
NR2R3), enone R1-CO-C(R2)=C(R3)R4, acyl halide (R-CO-X) in which
X represents the halide, acid anhydride (R1-CO-O-CO- R2) and imide 7. Gan C, Fan J, Liu L, Tian J, Jiao H, et al. (2013) Reconstruction of large
R1-CO-N(R2)-CO- R3 unilateral hemi-facial scar contractures with supercharged expanded forehead
flaps based on the anterofrontal superficial temporal vessels. J Plast Reconstr
Carboxyl group (or carboxy) is a functional group consisting of a Aesthet Surg 66: 1470-1476.
carbonyl (C=O) and a hydroxyl (OH) group, which has the formula 8. Velcheva I, Antonova N, Dimitrova V, Dimitrov N, Ivanov I (2006) Plasma lipids
-CO-OH or COOH. and blood viscosity in patients with cerebrovascular disease. Clin Hemorheol
Microcirc 35: 155-157.
Carboxylic acid is an organic acid in which at least one carboxyl 9. Scherp P, Hasenstein KH (2007) Anisotropic viscosity of the Chara (Characeae)
group is present. Its general formula is R-COOH, where R is some rhizoid cytoplasm. Am J Bot 94: 1930-1934.
monovalent functional group. The simplest examples of these groups
10. Gilbert SF (2005) Mechanisms for the environmental regulation of gene
are formic acid (H-COOH) and acetic acid (C-COOH). Acids with two expression: ecological aspects of animal development. J Biosci 30: 65-74.
or more carboxyl groups are called dicarboxylic, tricarboxylic, etc. The
11. Nuo P, Hernndez A, Mendoza-Figueroa T, Panduro A (1997) Viscosity
simplest dicarboxylic example is oxalic acid (COOH)2, which is just two regulates apolipoprotein A-1 gene expression in experimental models of
connected carboxyls. Other important natural examples are citric acid. secondary hyperlipidemia and in cultured hepatocytes. Biochim Biophys Acta
Salts and esters of carboxylic acids are called carboxylates. 1344: 262-269.
Esters are chemical compounds consisting of a carbonyl (CO) 12. Rezaee F, Peppelenbosch M, Dashty M (2013) Donor chimera model for
tolerance induction in transplantation. Hum Immunol 74: 550-556.
adjacent to an ether linkage (C-O-C). They are formed from the
reaction of an oxoacid (like carboxylic acid) with a hydroxyl compound 13. McMillan DE (1981) Physical factors important in the development of
atherosclerosis in diabetes. Diabetes 30: 97-104.
such as an organic alcohol or phenol. For instance, triglycerides are the
FA esters of glycerol. Esters are usually derived from an inorganic acid 14. Rezaee F, Dashty M (2013) Role of Adipose Tissue in Metabolic System
Disorders: Adipose Tissue is the Initiator of Metabolic Diseases. J Diabetes &
or organic acid in which at least one hydroxyl (-OH) group is replaced Metab S13: 008.
by an alkoxy (-O-alkyl) group, and most commonly from carboxylic
acids and alcohols. Esters are formed by condensing an acid with an 15. Back SH, Kaufman RJ (2012) Endoplasmic reticulum stress and type 2
diabetes. Annu Rev Biochem 81: 767-793.
alcohol.
16. Bagby SP (2004) Obesity-initiated metabolic syndrome and the kidney: a recipe
Ethers are organic compounds that contain an ether group. for chronic kidney disease? J Am Soc Nephrol 15: 2775-2791.
Ether group is an oxygen atom connected to two alkyl or aryl 17. Guilherme A, Virbasius JV, Puri V, Czech MP (2008) Adipocyte dysfunctions
linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol
groups (R1-O-R2) such as in anesthetic diethyl ether, (C-C-O-C-C). 9: 367-377.
Isoprene (or 2-methyl-1,3-butadiene) group is one of the common 18. Rogge MM (2009) The role of impaired mitochondrial lipid oxidation in obesity.
building blocks of the lipid structures with the formula C=C(C)C=C. Biol Res Nurs 10: 356-373.
Ketoacyl group (R-CO-C-CO-) is the other building block of the 19. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, et al. (2013)
Recruited brown adipose tissue as an antiobesity agent in humans. J Clin
lipid structure that consists of one acyl group (R-CO-) binding to one Invest 123: 3404-3408.
acetyl group (C-CO-).
20. Porter C, Brsheim E, Sidossis LS (2013) Does adipose tissue thermogenesis
Methyl group is a hydrocarbon group that is an alkyl derived from play a role in metabolic health? J Obes 2013: 204094.
methane, containing one carbon atom bonded to three hydrogen atoms 21. Ogasawara J, Sakurai T, Kizaki T, Ishibashi Y, Izawa T, et al. (2012) Higher
(CH3-). levels of ATGL are associated with exercise-induced enhancement of lipolysis
in rat epididymal adipocytes. PLoS One 7: e40876.
Oxoacids are acids that (i) contain oxygen (ii) contain at least one
22. Watt MJ, van Denderen BJ, Castelli LA, Bruce CR, Hoy AJ, et al. (2008)
other element, (iii) have at least one hydrogen atom bound to oxygen Adipose triglyceride lipase regulation of skeletal muscle lipid metabolism and
(iv) form an ion by the loss of one or more protons. insulin responsiveness. Mol Endocrinol 22: 1200-1212.
J Diabetes Metab
Page 17 of 19
23. Aloulou A, Carrire F (2008) Gastric lipase: an extremophilic interfacial enzyme 46. Murdoch SJ, Breckenridge WC (1995) Influence of lipoprotein lipase and
with medical applications. Cell Mol Life Sci 65: 851-854. hepatic lipase on the transformation of VLDL and HDL during lipolysis of VLDL.
Atherosclerosis 118: 193-212.
24. Dzieniszewski J, Gabryelewicz A (2003) Pancreas; pancreatitis--Polish
accomplishments. J Physiol Pharmacol 54 Suppl 3: 155-166. 47. Murdoch SJ, Breckenridge WC (1996) Effect of lipid transfer proteins on
lipoprotein lipase induced transformation of VLDL and HDL. Biochim Biophys
25. Dashti M, Kulik W, Hoek F, Veerman EC, Peppelenbosch MP, et al. (2011) A Acta 1303: 222-232.
phospholipidomic analysis of all defined human plasma lipoproteins. Sci Rep
1: 139. 48. Ezenwaka CE, Davis G (2000) Increased risk of cardiovascular disease in
newly diagnosed type 2 diabetic patients in a primary health care center in
26. Pankov D, Sprong H, Marois E, Thiele C, Eaton S (2005) Lipoprotein particles Trinidad. Diabetes Res Clin Pract 50: 137-145.
are required for Hedgehog and Wingless signalling. Nature 435: 58-65.
49. Dashty M, Akbarkhanzadeh V, Zeebregts CJ, Spek CA, Sijbrands EJ, et al.
27. Bijlsma MF, Peppelenbosch MP, Spek CA (2006) Hedgehog morphogen in (2012) Characterization of coagulation factor synthesis in nine human primary
cardiovascular disease. Circulation 114: 1985-1991. cell types. Sci Rep 2: 787.
28. Bijlsma MF, Spek CA, Peppelenbosch MP (2006) Hedgehog turns lipoproteins 50. Ross R (1993) The pathogenesis of atherosclerosis: a perspective for the
into Janus-faced particles. Trends Cardiovasc Med 16: 217-220. 1990s. Nature 362: 801-809.
29. Queiroz KC, Tio RA, Zeebregts CJ, Bijlsma MF, Zijlstra F, et al. (2010) Human 51. Ross R (1999) Atherosclerosis--an inflammatory disease. N Engl J Med 340:
plasma very low density lipoprotein carries Indian hedgehog. J Proteome Res 115-126.
9: 6052-6059.
52. Cesarman-Maus G, Hajjar KA (2005) Molecular mechanisms of fibrinolysis. Br
30. Bijlsma MF, Spek CA, Zivkovic D, van de Water S, Rezaee F, et al. (2006) J Haematol 129: 307-321.
Repression of smoothened by patched-dependent (pro-)vitamin D3 secretion.
PLoS Biol 4: e232. 53. Perdomo G, Henry Dong H (2009) Apolipoprotein D in lipid metabolism and its
functional implication in atherosclerosis and aging. Aging (Albany NY) 1: 17-27.
31. Queiroz KC, Bijlsma MF, Tio RA, Zeebregts CJ, Dunaeva M, et al. (2012)
Dichotomy in Hedgehog signaling between human healthy vessel and 54. Perdomo G, Kim DH, Zhang T, Qu S, Thomas EA, et al. (2010) A role of
atherosclerotic plaques. Mol Med 18: 1122-1127. apolipoprotein D in triglyceride metabolism. J Lipid Res 51: 1298-1311.
32. Bartelt A, Orlando P, Mele C, Ligresti A, Toedter K, et al. (2011) Altered 55. de Grooth GJ, Klerkx AH, Stroes ES, Stalenhoef AF, Kastelein JJ, et al. (2004)
endocannabinoid signalling after a high-fat diet in Apoe(-/-) mice: relevance A review of CETP and its relation to atherosclerosis. J Lipid Res 45: 1967-1974.
to adipose tissue inflammation, hepatic steatosis and insulin resistance. 56. Chatterjee C, Sparks DL (2011) Hepatic lipase, high density lipoproteins, and
Diabetologia 54: 2900-2910. hypertriglyceridemia. Am J Pathol 178: 1429-1433.
33. Raber J, Akana SF, Bhatnagar S, Dallman MF, Wong D, et al. (2000) 57. Funaki M (2009) Saturated fatty acids and insulin resistance. J Med Invest 56:
Hypothalamic-pituitary-adrenal dysfunction in Apoe(-/-) mice: possible role in 88-92.
behavioral and metabolic alterations. J Neurosci 20: 2064-2071.
58. Shachter NS (2001) Apolipoproteins C-I and C-III as important modulators of
34. Hoofnagle AN, Heinecke JW (2009) Lipoproteomics: using mass spectrometry- lipoprotein metabolism. Curr Opin Lipidol 12: 297-304.
based proteomics to explore the assembly, structure, and function of
lipoproteins. J Lipid Res 50: 1967-1975. 59. Yu YH, Ginsberg HN (2005) Adipocyte signaling and lipid homeostasis:
sequelae of insulin-resistant adipose tissue. Circ Res 96: 1042-1052.
35. Tzen JT, Lie GC, Huang AH (1992) Characterization of the charged components
and their topology on the surface of plant seed oil bodies. J Biol Chem 267: 60. Mead JR, Irvine SA, Ramji DP (2002) Lipoprotein lipase: structure, function,
15626-15634. regulation, and role in disease. J Mol Med (Berl) 80: 753-769.
36. Campos H, Perlov D, Khoo C, Sacks FM (2001) Distinct patterns of lipoproteins 61. Takasu S, Mutoh M, Takahashi M, Nakagama H (2012) Lipoprotein lipase as a
with apoB defined by presence of apoE or apoC-III in hypercholesterolemia and candidate target for cancer prevention/therapy. Biochem Res Int 2012: 398697.
hypertriglyceridemia. J Lipid Res 42: 1239-1249.
62. Sartippour MR, Renier G (2000) Differential regulation of macrophage
37. Campos H, Khoo C, Sacks FM (2005) Diurnal and acute patterns of postprandial peroxisome proliferator-activated receptor expression by glucose: role
apolipoprotein B-48 in VLDL, IDL, and LDL from normolipidemic humans. of peroxisome proliferator-activated receptors in lipoprotein lipase gene
Atherosclerosis 181: 345-351. expression. Arterioscler Thromb Vasc Biol 20: 104-2000.
38. Mahley RW, Innerarity TL, Rall SC Jr, Weisgraber KH (1984) Plasma 63. Staels B, Martin G, Martinez M, Albert C, Peinado-Onsurbe J, et al. (1996)
lipoproteins: apolipoprotein structure and function. J Lipid Res 25: 1277-1294. Expression and regulation of the lipoprotein lipase gene in human adrenal
cortex. J Biol Chem 271: 17425-17432.
39. Mulay V, Wood P, Rentero C, Enrich C, Grewal T (2012) Signal transduction
pathways provide opportunities to enhance HDL and apoAI-dependent reverse 64. Wang H, Eckel RH (2009) Lipoprotein lipase: from gene to obesity. Am J
cholesterol transport. Curr Pharm Biotechnol 13: 352-364. Physiol Endocrinol Metab 297: E271-288.
40. Rivellese AA, De NC, Di ML, Patti L, Iovine C, et al. (2004) Exogenous and 65. Kageyama H, Hirano T, Okada K, Ebara T, Kageyama A, et al. (2003)
endogenous postprandial lipid abnormalities in type 2 diabetic patients with Lipoprotein lipase mRNA in white adipose tissue but not in skeletal muscle
optimal blood glucose control and optimal fasting triglyceride levels. J Clin is increased by pioglitazone through PPAR-gamma. Biochem Biophys Res
Endocrinol Metab 89: 2153-2004. Commun 305: 22-27.
41. Adiels M, Olofsson SO, Taskinen MR, Born J (2008) Overproduction of very 66. Pedersen SB, Bak JF, Holck P, Schmitz O, Richelsen B (1999) Epinephrine
low-density lipoproteins is the hallmark of the dyslipidemia in the metabolic stimulates human muscle lipoprotein lipase activity in vivo. Metabolism 48: 461-
syndrome. Arterioscler Thromb Vasc Biol 28: 1225-1236. 464.
42. Austin MA, Hokanson JE, Edwards KL (1998) Hypertriglyceridemia as a 67. Sakayama K, Kidani T, Tanji N, Yamamoto H, Masuno H (2008) The synthesis
cardiovascular risk factor. Am J Cardiol 81: 7B-12B. and activity of lipoprotein lipase in the subcutaneous adipose tissue of patients
with musculoskeletal sarcomas. Anticancer Res 28: 2081-2086.
43. Merkel M, Eckel RH, Goldberg IJ (2002) Lipoprotein lipase: genetics, lipid
uptake, and regulation. J Lipid Res 43: 1997-2006. 68. Tisdale MJ (2009) Mechanisms of cancer cachexia. Physiol Rev 89: 381-410.
69. Dashty M (2013) A quick look at biochemistry: carbohydrate metabolism. Clin
44. Sarwar N, Danesh J, Eiriksdottir G, Sigurdsson G, Wareham N, et al. (2007)
Biochem 46: 1339-1352.
Triglycerides and the risk of coronary heart disease: 10,158 incident cases
among 262,525 participants in 29 Western prospective studies. Circulation 70. Morimoto C, Tsujita T, Okuda H (1998) Antilipolytic actions of insulin on basal
115: 450-458. and hormone-induced lipolysis in rat adipocytes. J Lipid Res 39: 957-962.
45. Frayn KN (1998) Non-esterified fatty acid metabolism and postprandial 71. Smith S, Witkowski A, Joshi AK (2003) Structural and functional organization of
lipaemia. Atherosclerosis 141 Suppl 1: S41-46. the animal fatty acid synthase. Prog Lipid Res 42: 289-317.
J Diabetes Metab
Page 18 of 19
72. Baranska J, Wojtczak L (1984) Transfer of phosphatidic acid between 96. Cho KJ, Shim JH, Cho MC, Choe YK, Hong JT, et al. (2005) Signaling pathways
microsomal and mitochondrial outer and inner membranes. Biochim Biophys implicated in alpha-melanocyte stimulating hormone-induced lipolysis in 3T3-
Acta 773: 23-31. L1 adipocytes. J Cell Biochem 96: 869-878.
73. Murad S, Kishimoto Y (1978) Chain elongation of fatty acid in brain: a 97. Langin D, Arner P (2006) Importance of TNFalpha and neutral lipases in human
comparison of mitochondrial and microsomal enzyme activities. Arch Biochem adipose tissue lipolysis. Trends Endocrinol Metab 17: 314-320.
Biophys 185: 300-306.
98. Hoffman BB, Chang H, Farahbakhsh Z, Reaven G (1984) Inhibition of lipolysis
74. Ye J, DeBose-Boyd RA (2011) Regulation of cholesterol and fatty acid by adenosine is potentiated with age. J Clin Invest 74: 1750-1755.
synthesis. Cold Spring Harb Perspect Biol 3.
99. Valet P, Berlan M, Beauville M, Crampes F, Montastruc JL, et al. (1990)
75. Goodridge AG (1972) Regulation of the activity of acetyl coenzyme A Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells
carboxylase by palmitoyl coenzyme A and citrate. J Biol Chem 247: 6946-6952. through a pertussis toxin-sensitive G protein. J Clin Invest 85: 291.
76. Foster DW (2012) Malonyl-CoA: the regulator of fatty acid synthesis and 100. Ishimoto K, Nakamura H, Tachibana K, Yamasaki D, Ota A, et al. (2009) Sterol-
oxidation. J Clin Invest 122: 1958-1959. mediated regulation of human lipin 1 gene expression in hepatoblastoma cells.
J Biol Chem 284: 22195-22205.
77. Xue B, Kahn BB (2006) AMPK integrates nutrient and hormonal signals to
regulate food intake and energy balance through effects in the hypothalamus 101. Lu B, Lu Y, Moser AH, Shigenaga JK, Grunfeld C, et al. (2008) LPS and
and peripheral tissues. J Physiol 574: 73-83. proinflammatory cytokines decrease lipin-1 in mouse adipose tissue and 3T3-
L1 adipocytes. Am J Physiol Endocrinol Metab 295: E1502-1509.
78. Jiang G, Zhang BB (2003) Glucagon and regulation of glucose metabolism. Am
J Physiol Endocrinol Metab 284: E671-678. 102. Reue K, Zhang P (2008) The lipin protein family: dual roles in lipid biosynthesis
and gene expression. FEBS Lett 582: 90-96.
79. Liljenquist JE, Bomboy JD, Lewis SB, Sinclair-Smith BC, Felts PW, et al. (1974)
Effects of glucagon on lipolysis and ketogenesis in normal and diabetic men. J 103. Donsmark M, Langfort J, Holm C, Ploug T, Galbo H (2004) Regulation and role
Clin Invest 53: 190-197. of hormone-sensitive lipase in rat skeletal muscle. Proc Nutr Soc 63: 309-314.
80. Ceddia RB, Bikopoulos GJ, Hilliker AJ, Sweeney G (2003) Insulin stimulates 104. Watt MJ, Steinberg GR, Chan S, Garnham A, Kemp BE, et al. (2004) Beta-
glucose metabolism via the pentose phosphate pathway in Drosophila Kc cells. adrenergic stimulation of skeletal muscle HSL can be overridden by AMPK
FEBS Lett 555: 307-310. signaling. FASEB J 18: 1445-1446.
81. Witters LA, Watts TD, Daniels DL, Evans JL (1988) Insulin stimulates the 105. Jensen MD, Haymond MW, Gerich JE, Cryer PE, Miles JM (1987) Lipolysis
dephosphorylation and activation of acetyl-CoA carboxylase. Proc Natl Acad during fasting. Decreased suppression by insulin and increased stimulation by
Sci U S A 85: 5473-5477. epinephrine. J Clin Invest 79: 207-213.
82. Kersten S (2001) Mechanisms of nutritional and hormonal regulation of 106. Gravholt CH, Mller N, Jensen MD, Christiansen JS, Schmitz O (2001)
lipogenesis. EMBO Rep 2: 282-286. Physiological levels of glucagon do not influence lipolysis in abdominal adipose
83. Yoshikawa T, Shimano H, Yahagi N, Ide T, memiya-Kudo M, et al. (2002) tissue as assessed by microdialysis. J Clin Endocrinol Metab 86: 2085-2089.
Polyunsaturated fatty acids suppress sterol regulatory element-binding protein 107. Miles JM, Jensen MD (1993) Does glucagon regulate adipose tissue lipolysis?
1c promoter activity by inhibition of liver X receptor (LXR) binding to LXR J Clin Endocrinol Metab 77: 5A-5B.
response elements. J Biol Chem 277: 1705-2002.
108. Bgin-Heick N (1987) The response of adenylate cyclase to ACTH in adipocyte
84. Nogalska A, Sucajtys-Szulc E, Swierczynski J (2005) Leptin decreases membranes of lean and obese mice. Mol Cell Endocrinol 53: 1-8.
lipogenic enzyme gene expression through modification of SREBP-1c gene
expression in white adipose tissue of aging rats. Metabolism 54: 1041-1047. 109. Hausman GJ, Wright JT (1994) The influence of hydrocortisone (HC) on
differentiation of adipose tissue is dependent on fetal age. Obes Res 2: 412-
85. Chao FF, Stiers DL, Ontko JA (1986) Hepatocellular triglyceride synthesis and
422.
transfer to lipid droplets and nascent very low density lipoproteins. J Lipid Res
27: 1174-1181. 110. Gate JJ, Clarke L, Bird JA, Lomax MA, Symonds ME (2000) Effect of feeding
level and thyroxine on adipose tissue development and growth in postnatal
86. Ahmadian M, Duncan RE, Jaworski K, Sarkadi-Nagy E, Sul HS (2007)
lambs. Exp Physiol 85: 439-444.
Triacylglycerol metabolism in adipose tissue. Future Lipidol 2: 229-237.
111. Kinoshita M, Ono K, Horie T, Nagao K, Nishi H, et al. (2010) Regulation of
87. Duncan RE, Ahmadian M, Jaworski K, Sarkadi-Nagy E, Sul HS (2007)
adipocyte differentiation by activation of serotonin (5-HT) receptors 5-HT2AR
Regulation of lipolysis in adipocytes. Annu Rev Nutr 27: 79-101.
and 5-HT2CR and involvement of microRNA-448-mediated repression of
88. Jaworski K, Sarkadi-Nagy E, Duncan RE, Ahmadian M, Sul HS (2007) KLF5. Mol Endocrinol 24: 1978-1987.
Regulation of triglyceride metabolism. IV. Hormonal regulation of lipolysis in
adipose tissue. Am J Physiol Gastrointest Liver Physiol 293: G1-4. 112. Gagnon A, Antunes TT, Ly T, Pongsuwan P, Gavin C, et al. (2010) Thyroid-
stimulating hormone stimulates lipolysis in adipocytes in culture and raises
89. Strlfors P, Belfrage P (1985) Phosphorylation of hormone-sensitive lipase by serum free fatty acid levels in vivo. Metabolism 59: 547-553.
cyclic GMP-dependent protein kinase. FEBS Lett 180: 280-284.
113. Schffler A, Schlmerich J, Buechler C (2006) The role of adipotropins and
90. Donsmark M, Langfort J, Holm C, Ploug T, Galbo H (2003) Contractions the clinical importance of a potential hypothalamic-pituitary-adipose axis. Nat
activate hormone-sensitive lipase in rat muscle by protein kinase C and Clin Pract Endocrinol Metab 2: 374-383.
mitogen-activated protein kinase. J Physiol 550: 845-854.
114. Gabbay RA, Lardy HA (1985) The antilipolytic effect of insulin does not require
91. Donsmark M, Langfort J, Holm C, Ploug T, Galbo H (2004) Contractions adenylate cyclase or phosphodiesterase action. FEBS Lett 179: 7-11.
induce phosphorylation of the AMPK site Ser565 in hormone-sensitive lipase in
muscle. Biochem Biophys Res Commun 316: 867-871. 115. Elks ML, Manganiello VC (1985) Antilipolytic action of insulin: role of cAMP
phosphodiesterase activation. Endocrinology 116: 2119-2121.
92. Daval M, Foufelle F, Ferr P (2006) Functions of AMP-activated protein kinase
in adipose tissue. J Physiol 574: 55-62. 116. Royo T, Pedragosa MJ, Ayte J, Gil-Gomez G, Vilaro S, et al. (1993) Testis
and ovary express the gene for the ketogenic mitochondrial 3-hydroxy-3-
93. Tansey JT, Sztalryd C, Hlavin EM, Kimmel AR, Londos C (2004) The central
role of perilipin a in lipid metabolism and adipocyte lipolysis. IUBMB Life 56: methylglutaryl-CoA synthase. J Lipid Res 34: 867.
379-385. 117. Buhman KF, Accad M, Farese RV (2000) Mammalian acyl-CoA: cholesterol
94. Ali YB, Carrire F, Verger R, Petry S, Muller G, et al. (2005) Continuous acyltransferases. Biochim Biophys Acta 1529: 142-154.
monitoring of cholesterol oleate hydrolysis by hormone-sensitive lipase and
118. Curtis R, Geesaman BJ, DiStefano PS (2005) Ageing and metabolism: drug
other cholesterol esterases. J Lipid Res 46: 994-1000.
discovery opportunities. Nat Rev Drug Discov 4: 569-580.
95. Harden RL, Oscar TP (1993) Thyroid hormone and growth hormone regulation
of broiler adipocyte lipolysis. Poult Sci 72: 669-676. 119. Pallottini V, Martini C, Cavallini G, Bergamini E, Mustard KJ, et al. (2007)
J Diabetes Metab
Page 19 of 19
Age-related HMG-CoA reductase deregulation depends on ROS-induced p38 122. Choi SH, Ginsberg HN (2011) Increased very low density lipoprotein (VLDL)
activation. Mech Ageing Dev 128: 688-695. secretion, hepatic steatosis, and insulin resistance. Trends Endocrinol Metab
22: 353-363.
120. Espenshade PJ, Hughes AL (2007) Regulation of sterol synthesis in
eukaryotes. Annu Rev Genet 41: 401-427. 123. Sharpe LJ, Brown AJ (2013) Controlling cholesterol synthesis beyond
3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). J Biol Chem 288:
121. Eberl D, Hegarty B, Bossard P, Ferr P, Foufelle F (2004) SREBP transcription 18707-18715.
factors: master regulators of lipid homeostasis. Biochimie 86: 839-848.
Submit your next manuscript and get advantages of OMICS

Group submissions
Unique features:
User friendly/feasible website-translation of your paper to 50 worlds leading languages

Audio Version of published paper
Digital articles to share and explore
Special features:
300 Open Access Journals

25,000 editorial team
21 days rapid review process
Quality and quick editorial, review and publication processing
Indexing at PubMed (partial), Scopus, EBSCO, Index Copernicus and Google Scholar etc
Sharing Option: Social Networking Enabled
Authors, Reviewers and Editors rewarded with online Scientific Credits
Citation: Dashty M (2014) A Quick Look at Biochemistry: Lipid Metabolism. J Better discount for your subsequent articles
Diabetes Metab 2: 324. doi:10.4172/2155-6156.1000324 Submit your manuscript at: www.editorialmanager.com/acrgroup
J Diabetes Metab

A Quick Look at Biochemistry Lipid Metabolism 2155 6156.1000324

Transféré par

Informations du document

Copyright

Formats disponibles

Partager ce document

Partager ou intégrer le document

Options de partage

Avez-vous trouvé ce document utile ?

Ce contenu est-il inapproprié ?

Droits d'auteur :

Formats disponibles

A Quick Look at Biochemistry Lipid Metabolism 2155 6156.1000324

Transféré par

Droits d'auteur :

Formats disponibles

Dashty, J Diabetes Metab 2014, 5:1

Diabetes & Metabolism http://dx.doi.org/10.4172/2155-6156.1000324

Review Article Open Access

A Quick Look at Biochemistry: Lipid Metabolism

Figure 1a: Abbreviations. Figure 1b: Abbreviations.

saturated fats are typically solid at room temperature, while highly

the simplest sphingolipids that result from the condensation of an

of glycerol. Fifty percent of TAG degradation happens by pancreatic

Retour of External Cholesterol in the Body

level of adipose triglyceride lipase (ATGL) gene expression in skeletal Lipoproteins

The level of LPL production in adipose tissue and the skeletal

Oxidation of FAs happens in two stages in the cytoplasm and in

Examples First stage: Each 17C-FA produces 7 2C-acetyl-CoA, which is

Fatty Acid Synthesis

molecule on the central SH to produce acetoacyl-ACP. Acetoacyl-ACP

regulation of TAG is lipin-1. It also has an effect on mitochondrial

Figure 10: Ketone bodies synthesis

of phosphodiesterase (PDE) that decreases the level of cAMP. Insulin,

group is a hydrocarbon and an alkyl derived from methane, containing Acknowledgement

Submit your next manuscript and get advantages of OMICS

User friendly/feasible website-translation of your paper to 50 worlds leading languages

300 Open Access Journals

Vous aimerez peut-être aussi