Resveratrol promotes the arcuate nucleus architecture remodeling to produce more anorexigenic neurons in high-fat-diet–fed mice

Adult hypothalamic neurogenesis has been considered a central regulator of energy balance. Resveratrol (RSV), a natural polyphenol, influences the body fat mass and reduces the amount of adipose tissue. The present study was designed to evaluate the effect of RSV on dynamic of hypothalamic neurons in a diet-induced obesity model of mice.Apoptosis, neurogenesis, the expression of the main trophic factors, and the fate of newborn cells were evaluated in the hypothalamus of adult male C57 BL/6 J mice fed a normal diet, a high-fat (HF) diet, or an HF diet supplemented with 400 mg/kg RSV (HF + RSV) for 6 wk.The HF diet caused an increase in neuronal apoptosis in the hypothalamus, which coincided with an increase in the number of newborn cells in the arcuate nucleus, suggesting that compensatory mechanisms developed to overcome deleterious effects of the HF diet. Addition of RSV to the HF diet enhanced the production of newborn cells in all studied regions of the hypothalamus. These changes were paralleled by enhancement of the expression of ciliary neurotrophic factor. Interestingly, a considerable proportion of newborn cells expressed neuropeptide Y in the arcuate nucleus of the HF group, and conversely, most of them differentiated to proopiomelanocortin neurons in HF + RSV mice.Diets rich in fat changed hypothalamic neuronal balance toward orexigenic versus anorexigenic neurons. Administration of RSV to the HF diet reversed this balance toward generation of anorexigenic neurons. These data point to the potential for RSV in regulation of body weight, possibly via modulation of hypothalamic neurogenesis.