Grant: Operating Grant

Obesity is a significant risk factor for several medical problems including diabetes and heart diseases, and therefore mortality. Lifestyle modification (caloric restriction and exercise) is the only therapy readily available to most obese patients. Unfortunately, the amount of weight loss is limited after lifestyle modification. Only one drug is currently approved for the long-term treatment of obesity in Canada. Therefore, there is a huge demand for a treatment protocol which can overcome the limitation of lifestyle modifications. Recent intensive studies suggest that a number of hormones produced by the gut play a critical role in the regulation of the metabolism and body weight. Xenin is one of the gut-produced hormones. Injection of xenin reduces food intake, body weight, fat mass, and increases levels of genes which stimulate a fat breakdown process called lipolysis. These findings led us to hypothesize that xenin stimulates lipolysis and xenin treatment reverses obesity and obesity-associated abnormal fat metabolism. To address this hypothesis, we propose to determine (1) the role of xenin in fat metabolism (more specifically, lipolysis), (2) the mechanism underlying the lipolysis-stimulating effect of xenin and (3) the beneficial effect of xenin treatment with or without caloric restriction in reversing obesity and obesity-associated abnormal fat metabolism. It is expected that the outcome of the proposed study will provide powerful information in establishing improved therapeutic protocol for the treatment of obesity and will have significant impact on the health of Canadians as well as residents in many other countries where obesity and obesity-associated impairments are serious health problems.