"The escalating epidemic of obesity, type-2 diabetes (T2D) and metabolic syndrome represents one of the most pressing and costly biomedical challenges confronting modern society. The impaired action of peripheral hormones like leptin, insulin and incretins on brain circuits controlling feeding and energy homeostasis (also known as ""central hormone resistance""), is increasingly recognized as playing a role in the pathophysiology of these disorders. Those hormones transmit information about the energy status of peripheral tissues, such as pancreas, liver, white and brown adipose tissue and gastrointestinal track.
These hormones reach their central brain targets by crossing the blood-brain barrier
at the level of microvessels or at circumventricular organs (CVOs) such as the median eminence, situated adjacent to the arcuate nucleus of the hypothalamus.
Appetite, energy balance, glucose and lipid metabolism are all partially controlled by select neurons located in the arcuate nucleus of the hypothalamus (ARH). However, much remains to be uncovered concerning the physiological mechanisms that control the access of blood-borne metabolic factors such as glucose and peripheral hormones to ARH neuronal circuits.
The laboratory where this project has been conducted (Development and Plasticity of the Neuroendocrine Brain, INSERM U1172, Lille, France) has raised the groundbreaking notion that tanycytes from the median eminence, a specific type of hypothalamic glial cells, act as ""gatekeepers"" that regulate the access of blood-borne signals to the hypothalamus, and in particular, their vesicular transport into the cerebrospinal fluid, from where they enter metabolic-hormone-sensitive regions.
The overall objective of the GLUCOTANYCYTES project is to elucidate the function of hypothalamic tanycytic barriers in the control of energy homeostasis with respect to glucose metabolism and peripheral hormone access to the hypothalamus."
