Grant: CIHR/Regional Partnership Program/Operating Grants

Obesity is a significant risk factor for several medical problems including diabetes and heart diseases, and therefore mortality. Although the cause of obesity is unclear, the brain areas called hypothalamus and brainstem play a critical role in the regulation of food intake and body weight. Recent intensive studies suggest that a number of hormones produced in the gut also play a critical role in the regulation of appetite and body weight by acting through brain cells in these areas. Xenin is one of gut-producing hormones. Injection of xenin reduces food intake and body weight gain in both normal lean and obese mice, suggesting the possibility that xenin could be a target for anti-obesity therapy. However, little is known about the mechanisms by which xenin exerts its effect on food intake. Although xenin is also present on the brain, the mechanism for the regulation of brain xenin activities is unknown. Therefore, the proposed study is designed (i) to investigate the regulation of brain xenin activity by nutritional status (e.g. feasting, feeding, and obesity) and (ii) to investigate possible mechanisms by which xenin regulates appetite via the brain. It is expected that the proposed study will enhance our understanding of the mechanism for the regulation of metabolism by xenin and facilitate subsequent investigations to establish an effective anti-obesity treatment by targeting the xenin system. Therefore, the proposed study may dramatically improve clinical outlook for patients with obesity and improve the health of Canadians.