YOUR GENETIC MAP AND HYPOTHALAMIC ARCHITECTURE DETERMINE YOUR BODY WEIGHT

These days, obesity is one of the major health problems in all societies. Obesity not only is a disorder but is considered as an important cause of several clinical concerns including cardiovascular diseases, cancers and diabetes mellitus. Despite various efforts, there is no definite strategy for controlling body weight and prevention of overweighting. On the other words, short term alleviation can be achieved following diet regimes but these programs failed in long term. It is important to note that obesity is a multifactorial disorder and several parameters play to a person become obese. On the other hand, body weight is a consequence of the balance between food intake and energy expenditure. Nowadays, scientists focus on personalized medicine in which the treatment plan for each person is individualized based on his/her molecular, cellular and finally behavioral characteristics. In this point of view, several nutritional examples can be considered. Multiple polymorphic genes encoding central and peripheral determinants of energy intake and expenditure have been revealed. People are different in taste preference as one of the major factors of food intake. There are several polymorphisms in the genes encoding taste receptors and a number of peripheral signaling peptides including insulin, leptin, ghrelin, cholecystokinin, and corresponding receptors. In addition, polymorphisms in the genes of central regulators of nutrition such as neuropeptide Y, agouti-related protein, melanocortin pathway factors, CART (cocaine- and amphetamine regulated transcript), some other neuropeptides, and their receptors has been reported over the past decade. Moreover, polymorphic genes encoding energy expenditure modulators (alphaand beta-adrenoceptors, uncoupling proteins, and regulators of adipocyte growth and differentiation) have been identified. Consequently, individual susceptibility to obesity strongly depends on the genetically determined patterns of energy balance regulation. On the other hand, the nutritional neuroscience focuses on the relation between nervous system and nutrition and vis versa. In this sense, not only multiple brain areas have a pivotal role in controlling of nutrition, but also the function of different brain areas involving in regulation of body weight are influenced by various nutrients. What is recently published interestingly is that a new niche of neural stem cells has been discovered near the wall of the third ventricle adjacent to hypothalamus the main center of body weight regulation. There are an active neurogenesis during life in this area and newborn cells including proopiomelanocortin (POMC) or neuropeptide Y neurons can be replaced in the hypothalamus. What is interesting is that the behavior of neural stem cells and consequently the change in hypothalamic architecture is affected by nutritional components. Specially, high-fat diet (HFD) change the behavior of the hypothalamic neural stem cells. The results of our recent study indicated that HFD, resveratrol (RSV) and calorie restriction (CR) diets have different effects on hypothalamic neurogenesis. 10 weeks consuming of HFD increased neurogenesis in dorsomedial hypothalamus (DMH) but didn’t any considerable effect on the fate of newborn cells in arcuate nucleus (ARC). These effects were seen parallel to increase in expression of hypothalamic BDNF. On the other hand, adding RSV to HFD from the 5th weeks of the study decreased weight gaining. I addition, adding RSV to HFD increased neurogenesis in ARC and lateral hypothalamus, although chow+RSV diet increased neurogenesis in ARC and ventromedial hypothalamus. These effects were coincidence with increase in expression of CNTF in hypothalamus. It is worth to point out that foods containing RSV changed the fate of newborn cells toward production of POMC+ neurons. What was interesting is that, CR decreased neurogenesis specifically in DMH. Although, the expression of CNTF in hypothalamus increased following CR consumption. Likewise, CR increased the generation of POMC+ neurons in ARC similar to RSV-containing foods. In conclusion, considering the molecular and cellular aspects of central regulation of body weight help us to identify the individual differences in hypothalamic response to various nutritional and non-nutritional signals. This area will introduce the promising approaches for definite treatment of obesity.