Project 466501

The prevalence of obesity has tripled since 1975, now affecting over 650 million adults worldwide. Obesity is linked to the development of multiple comorbidities including type 2 diabetes, cardiovascular disease, and impaired muscle tissue regeneration. A hallmark of obesity is the accumulation of excess fat in muscle tissues via intramuscular fat cells. How these diseased (obese) fat cells influence skeletal muscle repair is not well understood and is the focus of my research.In previous work, our groups established distinct in vitro models for (i) mimicking skeletal muscle repair, and (ii) inducing a diseased (obese) fat cell state. Here, I aim to bridge the gap between models by incorporating media harvested from obese fat cells (cell-conditioned media) into the skeletal muscle repair model to mimic the interaction between fat cells and muscle tissue. I hypothesize that adding media containing fat cell-secreted factors to muscle cell cultures will influence the efficiency of muscle repair.The effects of fat cell-secreted factors on skeletal muscle repair will be quantified via image analysis ;e.g. measuring muscle cell proliferation and size. Next, I will characterize the fat cell-conditioned media to uncover the specific factors responsible for altered skeletal muscle repair. Finally, I will extend our skeletal muscle-fat cell conditioned media model to screen for drugs that can enhance muscle repair. In summary, this proposal will establish a biologically relevant model to elucidate the influence of fat cells and their secretions on skeletal muscle repair. This model will improve our understanding of the molecular pathways that modulate muscle repair in individuals with obesity, helping to develop therapies for obesity-linked impaired muscle tissue regeneration.