Hypothalamic GHS-R in thermogenic regulation and diet-induced obesity
- View All
Obesity and insulin resistance threaten the health of millions of Americans. Obesity, in essence, is centered on fat tissues. There are two types of fat: white fat stores energy and brown fat burns energy. Increasing heat production in brown fat holds great promise for anti-obesity intervention.Ghrelin is a circulating hormone known to stimulate appetite and promote obesity. Ghrelin's effect is mediated by its receptor, GHS-R. We made global GHS-R knockout mice with the ghrelin receptor deleted in all tissues. We found that these mice are lean and more insulin-responsive due to that brown fat in these mice has greater heat production capacity. Brain is the most crucial site controlling of the heat producing function of brown fat, and the highest expression of GHS-R is detected in the brain. Thus we propose to test whether GHS-R deletion in specific brain regions enhances heat production of brown fat, thus protecting against obesity. We will use our newly-generated mice with GHS-R exclusively deleted in specific neurons to investigate the heat regulating effects of GHS-R in those neurons. The studies in this proposal will enable us to determine whether obesity can be reduced by the suppression of GHS-R in the brain. This proposal will also allow us to gain insight to whether GHS-R blockers have the potential to be a new class of anti-obesity drug to be used in the prevention and treatment of obesity and diabetes.