Nutritional State Affects the Expression of the Obesity‐Associated Genes Etv5, Faim2, Fto, and Negr1

Abstract

Obesity is a risk factor for type II diabetes, atherosclerosis, and some forms of cancer. Variation in common measures of obesity (e.g., BMI, waist/hip ratio) is largely explained by heritability. The advent of genome‐wide association studies (GWAS) has made it possible to identify several genetic variants that associate with measures of obesity, but how exactly these genetic variants contribute to overweight has remained largely unresolved. One first hint is given by the fact that many of the associated variants reside in or near genes that act in the central nervous system, which implicates neuronal signaling in the etiology of obesity. Although the brain controls both energy intake and expenditure, it has more capacity to regulate energy intake rather than energy expenditure. In environments where food is abundant, this renders the body prone to weight increases. To gain more insight into the neurobiological mechanisms involved, we set out to investigate the effect of dietary exposure on the expression levels of obesity‐associated genes in the ventro‐medial hypothalamus (VMH)/arcuate nucleus (ARC) and the substantia nigra (SN)/ventral tegmental area (VTA), two brain regions that are implicated in feeding behavior. We show that the expression of Etv5, Faim2, Fto, Negr1 but not Sh2b1 is affected by nutritional state in these two areas, thereby providing insight into the relationship between nutritional state and expression levels of obesity‐associated genes in two brain areas relevant to feeding.

A link between FTO, ghrelin, and impaired brain food-cue responsivity

“…First, Fto is highly expressed in brain regions controlling feeding and energy expenditure, such as the hypothalamus (1,15). Second, hypothalamic Fto expression is modulated by fasting (1,(16)(17)(18)(19)(20) and restricted access to food (21), although both upregulation (17,18) and downregulation (1,16,19) have been reported, apparently depending on the severity of caloric restriction. Exposure to a highfat diet also modulates hypothalamic Fto expression, with downregulation reported with short-term exposure (20) and upregulation with more prolonged exposure (22).…”

KRT13, FAIM2 and CYP2W1 mRNA Expression in Oral Squamous Cell Carcinoma Patients with Risk Habits

“…FAIM2 is also one of genes that associated with obesity. Obesity is a risk factor for type II diabetes, artheroclerosis, and some forms of cancer (Boender et al, 2012). Obesity (mainly due to excessive food intake) together with tobacco smoking and alcohol drinking are part of unhealthy lifestyle which could lead to development of cancer in later years.…”

Promoter methylation of fas apoptotic inhibitory molecule 2 gene is associated with obesity and dyslipidaemia in Chinese children

“…4 Subsequently, replicated study showed that rs7138803 was significantly associated with obesity in the Chinese population. 5 Although FAIM2 was regulated by nutritional state, 6 the molecular mechanism by which FAIM2 affects obesity has yet to be clarified.…”

“…5 Recently, some studies demonstrated that nutritional state affects the expression of FAIM2. 6 However, the mechanism by which FAIM2 is involved in obesity has yet to be elucidated. (Supplementary Figure 1).…”