Grant: Operating Grant - PA: Regional Partnership Program : Manitoba

Obesity is a significant risk factor for several medical problems including diabetes and heart diseases, and therefore mortality. Recent intensive studies suggest that a number of hormones produced by the gut and fat tissues play a critical role in the regulation of the metabolism and body weight by acting through brain cells. Xenin is one of the gut-producing hormones. Injection of xenin reduces food intake and body weight gain partly by increasing fat metabolism in both normal lean and obese mice. Gut hormones can interact with leptin, a fat cell hormone, to reduce appetite and body weight. These findings suggest the possibility that xenin can be a target for anti-obesity therapy. However, little is known about the mechanisms by which xenin exerts its effect on fat metabolism, fat mass, and body weight. Furthermore, it has not been tested whether xenin and leptin interact to regulate metabolism. Therefore, the proposed study is designed (i) to determine the role of xenin in the regulation of fat metabolism and (ii) to investigate the possible interaction between xenin and leptin in the regulation of fat metabolism and body weight in the mouse model of human obesity. It is expected that the proposed study will reveal a novel role for xenin in the regulation of metabolism, which has not previously been explored. It is also expected that the results of the proposed study will suggest a possible strategy to overcome the limitation of currently-available obesity therapies. Thus, the proposed project will provide powerful information in improving the health of Canadians, in particular those with obesity.