Glucose is the primary driver of hypothalamic POMC neurons. Here, we show that endothelial HIF-1α controls glucose uptake in the hypothalamus, and, that it is up-regulated in conditions of under-nourishment during which POMC neuronal activity is decreased. Endothelium-specific knockdown of HIF-1α impairs the ability of POMC neurons to adapt to the changing metabolic environment in vivo resulting in overeating of mice after food deprivation. The impaired functioning of POMC neurons was reversed ex vivo or by parenchymal glucose administration. These observations indicate an active role for endothelial cells in the central control of metabolism and suggest that central vascular impairments may cause metabolic disorders.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db16-1106/-/DC1.
- Received September 10, 2016.
- Accepted March 8, 2017.
- © 2017 by the American Diabetes Association.