Hypoxia-Inducible Factor Directs POMC Gene to Mediate Hypothalamic Glucose Sensing and Energy Balance Regulation

• DOI: 10.1371/journal.pbio.1001112
• Publication Date: 2011-07-26T20:42:51Z
• Authors: Hai Zhang; Guo Zhang; Frank J. Gonzalez; Sung-min Park; Dongsheng Cai
• Keywords: Proopiomelanocortin; Hypoxia-Inducible Factors; Hypoxia

Hypoxia-inducible factor (HIF) is a nuclear transcription that responds to environmental and pathological hypoxia induce metabolic adaptation, vascular growth, cell survival. Here we found HIF subunits HIF2α in particular were normally expressed the mediobasal hypothalamus of mice. Hypothalamic was up-regulated by glucose mediate feeding control hypothalamic sensing. Two underlying molecular pathways identified, including suppression PHDs metabolites prevent degradation recruitment AMPK mTOR/S6K regulate protein synthesis. activation directly POMC gene. Genetic approach then employed develop conditional knockout mice with inhibition neurons, revealing loss-of-function neurons impaired sensing caused energy imbalance promote obesity development. The effects independent leptin signaling or pituitary ACTH pathway. gene delivery counteracted overeating under conditions nutritional excess. In conclusion, controls direct central nutrient regulation body weight balance.