Grant: Project Grant

The pandemic increase in obesity is leading to serious obesity-related complications including diabetes, stroke, heart disease, infectious disease and many cancers. Two types of fat (adipose tissue) exist: white fat and brown fat. White fat store excess energy, while brown fat burns energy (thermogenesis). Impaired brown fat activity causes obesity in preclinical models and is associated with obesity in humans. Therefore, understanding the molecular determinants that control brown fat activation holds great promise in the fight against obesity. This proposal seeks to understand the underlying molecules that control a newly identified metabolic pathway in brown fat. Furthermore, the the health benefits of this pathway will be examined at the whole body level by using genetically engineered mouse models and by exploring the association of this pathway to human obesity. We have previously shown that creatine metabolism supports energy expenditure and is necessary to combat diet-induced obesity. However, the underlying mechanism that controls the anti-obesogenic action of creatine metabolism is not fully understood. This work will identify the molecular determinants that control creatine-dependent energy expenditure and will examine the role of these new molecules in regulating thermogenesis and providing protection from obesity. The proposed research has tremendous potential to discover new molecules that can be exploited therapeutically to combat obesity. Importantly, thermogenic brown fat has been found in humans, and so understanding how to activate this tissue has direct implications toward human health and well-being. The findings that come out of this proposal hold promise for improving the health of individuals and the population.