Obesity and obesity-associated inflammation are major risk factors for common, serious medical conditions including, metabolic syndrome, type II diabetes, atherosclerosis, non-alcoholic fatty liver disease, Alzheimer’s disease and diverse cancers. Obesity results from an imbalance between energy intake and expenditure. Further, diverse immune cells and mediators play important roles in modulating the response to excess dietary calories/fat, both centrally and peripherally. The inability to effectively target caloric intake or energy expenditure represents a fundamental therapeutic problem in obesity.
Current medical therapies are hampered by appreciable risks and/or meager long-term efficacy. We have uncovered a novel approach to target an immune-metabolic axis as a therapeutic to obesity via regulation of energy expenditure and adipose tissue lipid handling (lipolysis). Overall, the goals of our studies are to:
- Define the mechanisms underlying immune-regulation of energy expenditure and adipose tissue lipid handling in experimental models
- Validate and further define the role of these immune-metabolic axes in regulation of obesity and adipose tissue handling in humans.
Specifically, complementary approaches employing genetically modified mice, pharmacological tools and human samples (body composition, metabolic efficiency, mitochondrial function, lipolysis, glucose (dys)metabolism, (dys)lipidemia, WAT inflammation, modulation of transcription factors/networks associated with obesity) are used to define mechanisms of immune axes-mediated regulation of obesity and to provide proof of principal findings in humans. Importantly, as this pathway of immune action is clearly targetable, uncovering the mechanisms underlying immune axes-mediated regulation of obesity holds a significant promise for the development of novel therapeutic approaches.