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Student Name Professor Name Subject 8 May 2000 How obesity has become an epidemic problem through genetics Everybody probably knows what obesity is. We can see obese people in supermarkets, cafeterias, parks, hospitals and rarely in sport gyms. Nowadays obesity does not seem to be a big deal, however, it is. When an individual's body mass index, or BMI, is greater than 30, he or she is considered obese. Obesity is a term used to describe excessive, unhealthy body weight. This differs from the term "overweight" which is used to describe individuals with a BMI greater than 25 but lower than 30 and "morbidly" obese which refers to individuals who have a BMI greater than 40 or are more than 100 lbs. overweight (Nixon L., 2012). Obesity is a worldwide problem. More than one-third of U.S. adults (35.7%) are obese (Centers for Disease Control and Prevention, 2012). In the UK statistics shows 23%. The graph below shows percent of obese people in different populations.

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Obesity is a big issue for individuals, but unattractive reflection in the mirror is not the only problem. Overweight people as usual suffer from coming out diseases like heart diseases, troubles with breathing, complicated digestion processes and blood circulation. Medical professionals consider obesity a major risk factor for heart disease since obesity raises blood cholesterol levels, increases blood pressure levels and may induce or worsen diabetes. Obese individuals are also at risk for high cholesterol, diabetes, heart attacks, heart failure and hypertension, all of which are diseases and conditions that put individuals at risk for heart disease (Nixon L., 2012). With a wave of fast foods obesity seems to be a common disease. Unhealthy diet and lack of exercise as usual considered to be the main reasons of high body mass index, however not many people know that obesity predisposition can find its origin in genetics.

Yourlastname 3 To begin with, a genetic disease is any disease that is caused by an abnormality in an individual's genome. The abnormality can range from minuscule to major: from a discrete mutation in a single base in the DNA of a single gene to a gross chromosome abnormality involving the addition or subtraction of an entire chromosome or set of chromosomes. Some genetic disorders are inherited from the parents, while other genetic diseases are caused by acquired changes or mutations in a preexisting gene or group of genes. Mutations occur either randomly or due to some environmental exposure (Stppler M.,2012). The main reason of obesity on genetic level is a mutation or defect of certain DNA particle. Every gene is a carrier of certain information that builds our organism and is responsible for certain living processes in it. Being damaged or affected by any virus or physical disorder gene can not carry out its functions what causes to disorders in the form of disabilities, not correct function of organs and organ systems and diseases. Obesity can be considered as genetic disease. In fact, measures of fatness (also known as adiposity) are among the most heritable of human traits. Multiple studies of families, adoptees, twins and, most powerfully, adopted twin have all confirmed that heritable factors are likely to be responsible for 45-47% of the inter-individual variation in body mass index (the commonly used measure of adiposity) (Farooqi & ORahilly, 37) . There are several gene mutations (changes) that can cause obesity. These mutations also lead to the development of the second type of diabetes and other endocrine disorders. It is often

Yourlastname 4 associated with mutations in genes encoding proteins of the signaling system responsible for regulating the amount of energy stored as fat in the organism (Friedman J., 2012). The signaling system starts work with a protein named Leptin. Leptin is made by adipose tissue and sends a signal informing the brain that there are adequate stores of energy. When Leptin drops, appetite increases. Leptin activates a specific receptor (nerve endings) in the hypothalamus (part of the oldest structures in the brain), and includes the production of melanocortin, which reduces food intake by individuals. Referring to Genetic Factors in human obesity by Farooqi and ORahilly, lets examine several mutations that cause obesity. Congenital Leptin deficiency This is a rare syndrome associated with a mutation of the gene, moving t reading frame shifts of genetic information held in position G133 (map of the human genome is known almost entirely). Thus there is a modified form of Leptin, which is not affected by fat cells. Today there are hundreds of families with individuals with obesity caused by this mutation. Correction is achieved by Leptin injections. Congenital deficiency of the Leptin receptor This is a rare syndrome associated with a mutation of the leptin receptor in the hypothalamus. Thus there is a modified form of the receptor, which does not bind leptin. Today there are a few dozen families in the world carrying this mutation. Correction is unknown. Mutation of proopiometalokortin gene (POMC) With this mutation appears an altered form of the protein in which amino acid is replaced by glycine at position 236 (Arg236Gly). Occurs in about 1% among all cases of hereditary obesity forms.

Yourlastname 5 Mutation in the PC-1 gene The function of the protein encoded by this gene is forming of hormones ACTH and melanocortin, specifically cutting gene POMC. Thus, there are symptoms similar to mutations in gene POMC, with the only one difference hyperproinsulinemia. Hyperproinsulinemia is a disease where insulin is not sufficiently processed before secretion and immature forms of insulin make up the majority of circulating insulin immunoreactivity in both fasting and glucose-stimulated conditions (insulin immunoreactivity refers to all molecules detectable by an insulin antibody, i.e. insulin, proinsulin, and proinsulin-like material) (Diabetes Daily, 2012). And finally, mutation in receptor gene melanocortin type 4 (MS4R) The most commonly observed form of genetically caused obesity. Occurs in 6% of all obesity cases. There are around 15 different mutations in this gene. One of them is found in 95-99% of cases and affects about 1.3% of the human population. Obesity in carriers of all mutations listed above associated with overeating. People just do not get a signal on the adequacy of energy storage in the form of fat in adipose cells. Genetics of obesity is very complicated. It has variety of reasons, causes, consequences and methods of treatment. For instance, National Genetics Education and Development Center gives another genetic view about this issue. Researchers are nding genes that are associated with susceptibility to obesity. One such gene is FTO, dierent variants (alleles) of which might partly aect how much food people eat before they are satiated. There are two versions of FTO: the wild-type T allele and a slightly dierent A allele. Everyone has two copies of the FTO gene, so there are three possible FTO genotype combinations: TT, AT, and AA. People with AT have a 30% increased risk of being obese compared to a person with TT. An AA person has a

Yourlastname 6 70% increased risk of being obese compared to TT. This does not mean that AAs inevitably become obese, nor that TTs will never become obese. The FTO allele is just one factor that increases susceptibility to obesity. Knowledge of genotype might encourage patients to seek and comply with dietary advice. Understanding these mechanisms could lead to new obesity therapies. Even then, diet and nutrition will remain the most important part of patient care in this area.50% of the UK population are more likely to be obese because they have a particular variant of the melanocortin receptor gene MC4R (Geneticseducation.nhs.uk., 2008). The variant is more common in people of Indian-Asian ancestry which may partly explain high rates of obesity in this group. These gene variants also make people more likely to develop insulin resistance and type 2 diabetes. For many years people have been studying a problem of obesity. It led for numerous experiments and studies. There are many questions connected with obesity like: obese children, pregnancy and obesity, heredity of obesity, causes of obesity and aforementioned genetics of it. Heredity of obesity is a very interesting and important issue closely connected with genetics. Steave Morison referring to different studies writes in his article that many scientists have explored the role of heredity in determining human body shapes. Some researchers argue that obesity has a strong genetic determinant (it tends to run in families). They cite statistics showing that 80 percent of children having two obese parents are also obese. Twin Studies of identical twins who were separated at birth and raised in different environments have provided scientists with some of the most conclusive evidence to date that obesity may be an inherited trait. Whether raised in family environments with fat or thin family members, twins with obese natural parents tend to be obese in later life. According to another study, sets of identical twins who were separated and raised in different families and who ate widely different diets still grew up to

Yourlastname 7 weigh about the same. So, according to this information there can exist certain tendency to obesity, however, conditions particularly diet play not less important role. These studies contain the strongest evidence yet that the genes a person inherits are the major factor determining overweight, leanness, or average weight. Although the exact mechanics remain unknown, it is believed that genes set metabolic rates, influencing how the body handles calories. Some experts believe that this genetic tendency may contribute as much as 25 to 40 percent of the reason for being overweight. In the past decade, more and more research has pointed to the existence of a special "fat gene." The first and more likely to be one is the Db gene (for obesity), which is believed to disrupt the organisms satiety signaling system and may prompt individuals to keep eating past the point of being comfortably full. Research on Pima Native Americans, who have an estimated 75 percent obesity rate and nine in ten who are overweight, seems to point to an Ob gene that is a "thrifty gene." It is theorized that because their ancestors had to struggle through centuries of famine, their ancestor's basal metabolic rates slowed, allowing them to store necessary fats for survival. They may have passed these genes on to their children, explaining the lower metabolic rates found in Pimas today and their greater propensity for obesity. This case suggests a theory of evolution of metabolism. Scientists have found that they can manipulate mice genes and construct an Ob gene that will invariably lead to fatness in mice and to the development of diabetes II. Many suspect a human counterpart to this gene, but an actual gene formation has yet to be found. In addition, the (Beta)-3 adrenergic-receptor gene has been identified and found in human beings and mice. When mutated, it is thought to impede the body's ability to bum fat.

Yourlastname 8 Another group of scientists appear to have isolated a more direct route to appetite suppression, a protein called GLP-l, which is known to slow down the passage of food through the intestines to allow the absorption of nutrients. When scientists injected GLP-l into the brains of hungry rats, the rats stopped eating immediately. Are leptin and GLP-l key factors in appetite suppression? It is speculated that leptin and GLP-l might play complementary roles in weight control. These experiments prove that proteins such as GLP-1, leptin and hormones play if not basic, but at least primary role in heredity of obesity and its genetics. Talking about heredity and genetic information we automatically think about the next generation which inherits all the traits that we are discussing here. Childhood obesity has become a global problem of the 21st century. The prevalence has increased at an alarming rate. Globally, in 2010 the number of overweight children under the age of five is estimated to be over 42 million. Close to 35 million of these are living in developing countries (World Health Organization, 2012). It is not a secret that obese children are more likely to have serious problems with their health in young age, however it is easier to cure and even prevent obesity in such a young age. The latest information about childrens obesity is not very cheering. The latest report about obesity and genetics study regarding to children by Malcolm Ritter states that some children get severely obese because they lack particular chunks of DNA, which kicks their hunger into overdrive. The British researchers checked the DNA of 300 children who'd become very fat, on the order of 220 pounds by age 10. They looked for deletions or extra copies of DNA segments. They found evidence that several rare deletions may promote obesity, including one kind they studied further and found in less than 1 percent of about 1,200 severely obese children. That deletion, on chromosome 16, apparently causes trouble because it removes a gene that the brain

Yourlastname 9 needs to respond to the appetite-controlling hormone leptin. Dr. Sadaf Farooqi of Cambridge University, author of numerous works such as Genetic Factors in Human Obesity, 2007 supports this theory. Dr Farooqi has been a Consultant Physician at Addenbrookes Hospital, Cambridge since 2006. Since that time, she has been promoted to Reader and now to Professor in recognition of her research achievements and contributions to clinical practice and teaching at a local, national and international level. Now Dr Farooqi has been promoted to Professor of Metabolism and Medicine at the University of Cambridge (Genetics Of Obesity Study, 2012). She made a big contribution in discoveries and scientific researching of obesity. Valuable evidence is the website of the Institute of Metabolic Science of the University of Cambridge where Dr Farooqi reports about the research goals and methods: The long term goal of our research is to understand the molecular and physiological pathways involved in the regulation of human appetite and body weight. To this end, we use a number of complementary genetic strategies to study over 4000 patients we have recruited with the help of many international collaborators to the Genetics of Obesity Study (GOOS).We have shown that mutations that effect the adipocyte-derived hormone leptin and its hypothalamic targets cause severe early onset obesity in 8% of the GOOS cohort. In addition to pursuing new candidate genes, we are using hypothesis free approaches including SNP-arrays and whole exome sequencing to identify novel rare genetic variants. We play a major role in the UK10K consortium which aims to identify rare variants in health and disease (www.uk10k.org). These approaches are leading to the discovery of novel obesity genes whose function we study using a number of molecular and cellular appraoches. In particular, we are developing the use of patient specific neural cell lines derived from inducible pluripotent

Yourlastname 10 stem cells (obtained from fibroblasts) as a model system for investigating molecular mechanisms and for drug discovery. We undertake physiological studies in cohorts of patients and volunteers to examine the role of the relevant molecules in eating behaviour, energy expenditure and peripheral metabolism. This integrated approach has allowed us to demonstrate the importance of specific molecular pathways in the development of severe obesity which can be considered a neurobehavioural disease. In collaboration with Professor Paul Fletcher, we have a major interest in using functional MRI to study the pattern of brain activation involved in aspectsof eating behaviour, such as food reward and motivation. To date, our work has allowed us to provide improved diagnostics for a range of obesity syndromes. We have been able to provide a mechanism based treatment for one of these disorders, congenital leptin deficiency, where we successfully treat patients from around the world. Our overall aim is to make a major contribution to the design of pharmacological, nutritional and behavioural interventions to benefit patients with severe obesity. Scientists understanding all the importance of the question of obesity carry out different experiments. Article by Roxanne Khamsi tells about Frances Ashcroft at the University of Oxford, UK and her collaborators who took a close look at the sequence of the gene called FTO. As I have previously mentioned FTO is a gene that makes people vulnerable to obesity, it also produces a protein that may directly modify DNA in a region of the brain known to control food intake. So using a complex algorithm, they searched for similar sequence fragments within the human genome.

Yourlastname 11 The hunt for possible matches revealed that the FTO gene most closely resembles the genetic sequence of the 2-OG oxygenase family of proteins. These proteins have several roles, including the repair and modification of DNA. Altered genes Ashcroft and her colleagues synthesized the FTO protein in the laboratory using the human sequence and mixed the protein with single-stranded DNA in a test tube. They found that the protein removed chemical markers on the DNA, known as methyl groups. This is significant, as the addition and removal of methyl groups can act to switch genes on or off, so altering their activity. This process is known as epigenetic change. The researchers believe that the FTO protein may somehow modify the activity of genes involved in metabolism and fat storage, which in turn may influence a persons risk of obesity. In another part of the new study, researchers examined the brains of mice designed to produce fluorescent FTO proteins. They found high concentrations of the protein in the rodents hypothalamus, a region of the brain that helps regulate hunger. Ashcroft says it is still unclear how the FTO protein directly influences appetite, but it could possibly be exerting influence by altering the activity of other genes. Alan Herbert, a geneticist at the Boston University School of Medicine in Boston Massachusetts, US, promoted a very interesting view: Certain FTO variants might work in the brain to increase fat storage throughout the body. But he stresses that these variants could have been helpful for our ancestors, who had less reliable food supplies. At some point in history, it was likely advantageous to efficiently store calories. (Herbert A, 2007).

Yourlastname 12 No less seriously obesity addresses problems of phycology and pregnancy. First I would like to discuss psychological points of obesity since they are directly connected with society. As usual obese people experience constant stress since they stand out among others. Individuals with obesity are misunderstood; people are used to consider obesity as lack of self-control and weakness not even thinking that the reason can hide in genetic. People with high BMI can not afford themselves simple entertainments such as active games, dancing parties, hanging out in crowded places because there is a big possibility to face inadequate reaction of some people. According to Langone Medical Center a 1991 study showed that 80 percent of severely obese people: perceive themselves as physically unattractive believe that others make disparaging comments about their weight dislike being seen in public feel discrimination when applying for jobs feel that they are treated disrespectfully by their physician

These facts are more distressing if to remember that obesity occurs among young people and teenagers who react more sensitively at surrounding factors. Much more relevant is the teasing, taunting and poor treatment they receive from other children at school and in the community. And for many, its not only how others think of them, but how they think of themselves. A sizable percentage of overweight kids particularly girls are clinically depressed as a result of a preoccupation with being overweight. This issue is enough dangerous. According to overweightteen.com, recent survey reveals that obese children rate their quality of life as low as those of young cancer patients undergoing chemotherapy. Other studies are reporting increased rates of depression, low self-esteem and social isolation, which are then manifest in significant

Yourlastname 13 behavioral problems. As these children grow up, they are less likely to be accepted into college, less likely to get married, and more likely to occupy a lower socioeconomic status. Another individuals who may react sharply are pregnant women. A study reported by Barbara Luke of Michigan State University looked at pregnancy rates in 50,000 women undergoing assisted reproductive technology procedures. The study showed that women with a body mass index (BMI) of over 40, compared to the normal BMI of 18.5 to 24.9, were 35 percent less likely to become pregnant. Being overweight doesn't mean you can't get pregnant, but it does mean it might be more difficult than it would be otherwise (Perkins S.,2010). In general during pregnancy women experience different changes and complications, but obesity increases the risk of having a number of pregnancy complications. According to the information of Royal Womens Hospital (Australia) problems that obese pregnant women can face include: gestational diabetes - a form of diabetes that developes during pregnancy pre-eclampsia - a condition that only occurs in pregnancy, characterised by hypertension (high blood pressure) and the presence of protein in the urine abnormalities of the baby's growth, development and general health sleep apnoea - a condition that causes you to temporarily stop breathing while you are sleeping. failure to progress in labour shoulder dystocia (the shoulders get stuck during birth) difficulties monitoring the baby's heart difficulties with providing satisfactory pain relief in labour increased risks with attempted vaginal birth after caesarean section need for an emergency caesarean section

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The problems with operating on women with obesity include the following: positioning, because woman is unable to lie flat and to be moved if an emergency arises an epidural or spinal anesthetic is more difficult to site correctly and is more likely to dislodge or fail it is more difficult to maintain airways (especially in the emergency setting) the procedure is more difficult extra monitoring is required woman may require admission to an intensive care unit after the operation.

In spite of all complications that obesity brings and all intricacy of its genetics, it is still possible to escape obesity or at least ease daily life and strengthen your health. There are several principles of daily ratio and principles that can help to keep your body mass index stable. The main and most important step is to control the diet. Nutrition is a basic living process of all leaving creatures; at the same time, realizing all importance of diet, not everyone controls own daily food ration. All biomolecules in the organism should be balanced; carbohydrates, proteins, nucleotides, and lipids have certain function and need to be consumed by organism in specific quantity and certain day time. Otherwise, overabundance or deficiency of any organic molecule can cause a dysfunction on any bodys level, beginning with cell functions and ending with organ systems and immunity. Obese people should escape overeating and eating late at night. Also it is necessary to avoid food with high content of sugar carbohydrates, which have tendency to be stored by organism. Another important tip is counting of calories. Calorie needs are different for every individual based on gender, body size and activity level. Obese people

Yourlastname 15 need more calories than normal weight people. An obese adult woman needs 1800-2000 calories per day and an obese man needs 2000-2400 calories per day. If weight loss is desired it is recommended to decrease your intake by 300-500 calories per day. It is important not to consume less than 1200 calories per day (Marchini M., 2010). So it is necessary to keep track of what you eat, how much and when. It is a fact that obese people because of genetic dysfunction can not control feel of hunger, but it is possible to figure out how much food the organism needs per day. And it is important to remember that one piece of pie costs 30 minutes at trade meal. Second step is daily activity. Lack of exercise is harmful for people with normal weight, so obese people need exercising in their life. Hard weightlifting is not the best variant. As usual obese people should pick cardio and anaerobic exercises for themselves. It may be hard for the first time, but it is possible to include activities in daily life: stairs instead of elevator, walking instead of car, walking with a dog or bike ride instead of TV. However, it is important to remember, that there are certain risks associated with any exercise routine, and if you're obese, your risks may increase accordingly, depending on your weight and other health issues. Exercise can injure joints, tear muscles and other soft tissue, increase your blood pressure and heart rate and cause a variety of breathing problems. Take precautions and let your trainer know ahead of time about any health conditions (Bardot J., 2012). Exercise may produce an increase in heart rate and blood pressure as well as cause problems if you experience peripheral artery disease, or PAD. Obesity can cause the veins in the legs to malfunction, causing bruising, pain and ulceration of the calves and feet. A common symptom of PAD is experiencing pain in the legs and feet after exercise.

Yourlastname 16 So to escape traumatic moments and injures, the best alternative is to vary daily activity and to ask professional coach for advice if you feel that you are not ready to exercise on your own. Nowadays there is a variety of health programs in health centers, gyms or swimming pools. In conclusion, relying on all facts, we can see that obesity is a worldwide issue that afflicts different populations among adults and children. There are several reasons of this disorder in the internal organisms system. Inordinate food consumption such as overeating and immobility are widely known causes. At the same time obese people face big stress and disrespectful attitude of the society, since not many people know that genetic is a common root of obesity. Statistics states that this case occurs in 6% of human obesity. Obese people suffer from diseases that can develop because of high BMI: cardiac failure, breathing problems, thrombophlebitis, low immunity etc. Genetic disorder can be caused by lack of hormone leptin, deformation of proteins and genes responsible for signal system connected with food consumption and storage of organic biomolecules. Scientists confirm that heredity plays not the last role in obesity predisposition. Families with obese members of family are more likely to grow descendants with extra BMI. Obesity leads to number of problems of different character psychological, physical and pregnancy problems which cause stress for women. On genetic level it is hard to cure, however scientists till today work hard on experiments and researches how to prevent or stop genetic obesity. On the other hand if you have certain obesity level it is possible to stay in healthy condition if to keep certain level of daily activity and nutrition diet. There are many ways to stay in shape even with obesity, nowadays have been developed lots of exercising programs for obese people, so it is possible to pick your own according to your level and body condition. So progress in medical world can cheer us up, because we have enough information about obesity and we know that scientists are still working on this question.

Yourlastname 17 Works Cited Centers for Disease Control and Prevention. Overweight and Obesity, 2012. <http://www.cdc.gov/obesity/data/adult.html> Nixon Lindsay, Deaths from Obesity & Heart Disease, 1999-2012. <http://www.ehow.com/about_5422133_deaths-obesity-heart-disease.html> Stppler C.Melissa, Genetic Diseases Overview, 1996-2012. <http://www.medicinenet.com/genetic_disease/article.htm> NationMaster.com, Health Statistics, 2003-2012. <http://www.nationmaster.com/graph/hea_obe-health-obesity> National Genetics Education and Development Center, Genetics and Obesity, Supporting Genetics Education for Health, 2008. <http://www.geneticseducation.nhs.uk/media/32898/obesity-factsheet.pdf> Diabetes Daily, Hyperproinsulinemia, 2005-2012. <http://www.diabetesdaily.com/Hyperproinsulinemia> Steave Morison, Obesity and Heredity,2009. <http://ezinearticles.com/?Obesity-and-Heredity&id=2945989> World Health Organization (WHO), Childhood overweight and Obesity, 2012. <http://www.who.int/dietphysicalactivity/childhood/en/> Malcolm Ritter, Obesity and Genetics Study Finds Missing DNA Can Promote Childhood Obesity, 2012. <http://www.huffingtonpost.com/2009/12/07/obesity-and-genetics-stud_n_383127.html> Genetics of Obesity Study (GOOS), Dr Sadaf Farooqi, 2012. <http://www.goos.org.uk/resource-centre/latest-news/46-dr-sadaf-farooqi>

Yourlastname 18 Farooqi Sadaf, Institute of Metabolic Science, Institute of Cambridge, Research Interests, 2011. <http://www.mrl.ims.cam.ac.uk/staff/PI/Farooqi/> Roxanne Khamsi, Obesity gene may alter brain DNA, 2007. <http://www.newscientist.com/article/dn12893-obesity-gene-may-alter-brain-dna.html> NYU Langone, NYU Langone Weight Management Program, Psychological Effects of Obesity, 2012. <http://thinforlife.med.nyu.edu/surgical-weight-loss/obesity/psychological-effects-obesity> overweightteen.com, The Psychological Consequences of Obesity in Children and Teens, 2010. <http://www.overweightteen.com/psychological.html> Sharon Perkins, How to Get Pregnant If You Are Fat, 2010-2012. <http://www.livestrong.com/article/72816-pregnant-fat/> The Royal Womens Hospital (Victoria Australia), Obesity and pregnancy, 2006-2008. <http://www.thewomens.org.au/Obesityandpregnancy> Markee Marchini, Diet Plan For An Obese Person, 2010-2012. <http://www.livestrong.com/article/209940-diet-plan-for-an-obese-person/> Jean Bardot, Exercising Dangers For Obese People, 2012. <http://www.livestrong.com/article/554136-exercising-dangers-for-obese-people/>

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