Molly Crenshaw

Dr. P

NUTR 346

Vitamin A Paper Review

22 January 2018

In the abstract, the process of vitamin A metabolism is explained. The majority of beta-

carotene is metabolized in the intestines by an enzyme called BC01. Beta-carotene is converted

to retinaldehyde by this enzyme in the intestines, then is broken down to form retinol, or vitamin

A, then packaged into a chylomicron, then distributed throughout the body. Some are involved in

retinoic acid synthesis on-site, which has an effect on gastrointestinal immunity.

The author’s claim is that there is a protein called ISX that is essential to control the

metabolism of beta-carotene throughout this process of vitamin A metabolism. ISX mediates the

gap between immunity and diet. If the regulation of metabolism is not tightly controlled,

inflammatory disorders in humans occur and are caused by “polymorphisms in the ISX gene”

(Widjaja-Adhi). The author also claims that excessive vitamin A intake can lead to inflammatory

responses when excess retinoid stores are stored in large lymphocytes.

Other points in this paper discuss how the ISX genotype affects immune homeostasis in

this intestines and that ISX is necessary in order to “maintain vitamin A homeostasis in response

to dietary beta-carotene” (Widjaja-Adhi). Also, the studies showed that when maternal mice

were supplemented with beta-carotene, the lymphoid size and number increased in their ISX-

deficient offspring. The vitamin was transferred to the embryo through the maternal blood stream

and the follicles of the offspring of supplemented mice were larger in size and number. The last

points the author makes is how ISX-deficient mice show a development of impaired glucose
metabolism, insulitis due to loss of tolerance against antigens, and how dietary beta-carotene

causes insulin resistance.

In this test, the author uses certain tests to prove their claim. In ISX-deficient mice,

BCO1 expression was uncontrolled and “led to increased retinoid production in the intestine”

(Widjaja-Adhi). In mice, an increase in beta-carotene led to the expression of Aldhla2, Dhrs3,

and Cyp26a1 genes as well as Ccr9 (chemokine receptor). The phenotype expressed was

associated with increased lymphocytes in the intestines. This large number of lymphocytes

“accumulated in large lymphoid follicles” (Widjaja-Adhi). With the increased amount of retinoid

production in the intestines, this caused an increase in retinoid stores in hepatic tissues. This

increase in production led to the disruption of retinoid homeostasis. This disruption then affected

lymphocyte differentiation and was associated with pancreatic insulitis glucose intolerance. As

stated above, the excessive consumption of vitamin A can also cause inflammatory responses.

Therefore, beta-carotene utilization must also be tightly controlled in order to prevent

inflammatory diseases.

In the abstract, the overview of what this test consisted of was that because of an increase

in BCO1 (which metabolizes beta-carotene), there was an increase in retinoid production. With

this increase, homeostasis was disrupted. This disruption affected lymphocyte differentiation and

caused insulitis and glucose intolerance. This lead to the conclusion that vitamin A metabolism

needed to be tightly regulated because of the relation between diet and immunity. In the

“significance” box, the relation between the intestines and nutrient absorption is explained. The

majority of nutrients are absorbed through the intestines. As well as being the place to absorb

essential nutrients, it is also a barrier that protects against toxins and antigens. Because of this,

the majority of lymphocytes in the body reside here. The protein ISX is an important mediator
between immunity and diet. This protein regulates the production of vitamin A that comes from

the diet. If there is no control over this regulation, vitamin A homeostasis is disrupted, thus

impairing immunity.

The conclusion was that diet and immunity are linked together: vitamin A metabolism

must be tightly regulated. Also, this study showed evidence that ISX is an important part of

maintaining strong immunity and tolerance in the intestinal barrier. In order to prevent

disruptions in lymphocyte differentiation and retinoid homeostasis, retinoid production through

the metabolism of beta-carotene must be tightly controlled. With this regulation, inflammatory

responses are less likely to occur, thus decreasing the risk for inflammatory diseases.

This paper relates to the discussion through class because it is discussing the metabolism

of vitamin A. We have learned the overall process of how vitamin A is metabolized, but this

paper gives a real-life example of how the knowledge of metabolism is used in research. We are

given the outline of how vitamin A is absorbed, but with this paper, we are able to see the details

and can apply what we already know to how it can be applied through different experiments.

Through this research, we can know more about vitamin A, its effect on immunity, and the

importance it has in the prevention of inflammatory disease.