Project 461441

Obesity is associated with an increased risk for cardiovascular diseases, diabetes, and metabolic syndrome. Recently, we discovered that obesity is also associated with muscle, bone, and joint degeneration, and identified that the release of inflammatory mediators from fat deposits and from the intestines are likely causes for the degeneration of these tissues. In order to identify the role of fat- and intestine-released inflammatory agents on musculoskeletal tissue degeneration, we will be using exercise and diet interventions to systematically change the release of targeted inflammatory agents and determine the effects of these interventions on muscle, bone and joint health. We hypothesize that carefully administered, and well timed dietary and exercise interventions, alter the release of inflammatory mediators, thereby reducing or preventing obesity-associated degeneration of musculoskeletal tissues. Our studies are performed on a well-established diet-induced obesity model in rats that results in fat infiltration into muscles, bone lesions, and osteoarthritis of the knee. We anticipate that the lessons learned in this animal model will inform clinical trials in humans with obesity who are at risk of muscle (sarcopenia, fat infiltration, and fibrosis), bone (osteopenia) and joint degeneration (osteoarthritis). These musculoskeletal diseases are among the primary causes for reduced mobility and loss of quality of life. Our work has the general aim of improving mobility across the lifespan for all.