Project 444489

Obesity, which will be affecting a third of global population in 2025, is a major health problem with increased risk for various chronic diseases. Recent studies from my lab identified the IRX3 and IRX5 genes as two major risk factors involved in human obesity. The hypothalamus of our brain controls appetite (and the food intake we consume) as well as metabolic rate (and how we burn excess energy intake). Our data suggest that IRX3 and IRX5 regulate food intake by modulating the formation of new leptin-sensing neurons in the hypothalamus (After meals, leptin is a hormone secreted by adipocytes to signal satiety). Importantly, we found that IRX3 and IRX5 appear to control the activities of a novel population of neural stem cells in postnatal mouse hypothalamus. In this proposal, we propose molecular genetic experiments using various mouse models to investigate the molecular actions of IRX3 and IRX5 in these hypothalamic neural stem cells. The proposed research could provide useful knowledge for potential intervention of eating disorder, obesity and related metabolic diseases.