GLUT2 expression by glial fibrillary acidic protein-positive tanycytes is required for promoting feeding-response to fasting.

Feeding behavior is a complex process that depends on the ability of the brain to integrate hormonal and nutritional signals, such as glucose. One glucosensing mechanism relies on the glucose transporter 2 (GLUT2) in the hypothalamus, especially in radial glia-like cells called tanycytes. Here, we analyzed whether a GLUT2-dependent glucosensing mechanism is required for the normal regulation of feeding behavior in GFAP-positive tanycytes. Genetic inactivation of Glut2 in GFAP-expressing tanycytes was performed using Cre/Lox technology. The efficiency of GFAP-tanycyte targeting was analyzed in the anteroposterior and dorsoventral axes by evaluating GFP fluorescence. Feeding behavior, hormonal levels, neuronal activity using c-Fos, and neuropeptide expression were also analyzed in the fasting-to-refeeding transition. In basal conditions, Glut2-inactivated mice had normal food intake and meal patterns. Implementation of a preceeding fasting period led to decreased total food intake and a delay in meal initiation during refeeding. Additionally, Glut2 inactivation increased the number of c-Fos-positive cells in the ventromedial nucleus in response to fasting and a deregulation of Pomc expression in the fasting-to-refeeding transition. Thus, a GLUT2-dependent glucose-sensing mechanism in GFAP-tanycytes is required to control food consumption and promote meal initiation after a fasting period.

Tanycytes: a gateway to the metabolic hypothalamus.

The central regulation of energy balance relies on the ability of the brain to promptly and efficiently sense variations of metabolic state. To achieve this, circulating hormonal and metabolic signals have to cross the blood-brain interface, where unusual glial cells named tanycytes have been described to play a key role in this process. Tanycytes are specialised polarised ependymoglial cells that line the floor of the third ventricle and send a single process to contact hypothalamic neurones and blood vessels. Although their role in the regulation of energy balance via the modulation of neuronal activity or their chemosensitivity has been already described, recent studies ascribe a new function to tanycytes in the regulation of energy homeostasis as a result of their capacity to regulate the access of metabolic signals to the hypothalamus. This review discusses the peculiar place of tanycytes within the blood-hypothalamus interface, as well as a striking capacity to remodel their own interface to ensure an adaptive metabolic response to energy imbalances.