Diabesity and hormonal resistance: role of the tanycytic barrier at the blood-metabolic hypothalamus interface – gliodiabesity

The incidence of obesity rises in France as in other industrialized nations. Since administration of leptin and insulin to rodents decreases food intake and increases energy expenditure, resulting in loss of fat mass, these adiposity signals initially were hailed as a potential cure for obesity. Obese individuals have elevated circulating leptin and insulin levels. However, it fails to mediate weight loss, suggesting that most forms of human obesity are hormonal resistant. Our work suggest that the median eminence of the hypothalamus is a key site for the uptake of peripheral signals traveling in the pituitary portal circulation, a mechanism that may be utilized by the metabolic brain to control adiposity signals targeting at the arcuate nucleus of the hypothalamus that distributes their effects centrally. This transport involves a peculiar glial cell type named tanycytes. The goal of our future studies is to investigate the role of leptin and insulin in development and plasticity of this exchange area and, conversely, to determine whether disruption of its functional integrity renders the organism prone to develop metabolic disorders'. We also propose to investigate the influence of altered nutrition on function of the tanycytic barrier at the median eminence, as well as to measure the consequences of the selective impairment of this barrier on energy homeostasis, during adulthood.