Adipose tissue inflammation directly contributes to the overall inflammatory state in obesity, with immune cells being intimately involved regulating adipocyte function and vice versa. The cytokine, oncostatin M (OSM), is produced by adipose tissue macrophages. Our published data suggests that lack of OSM signaling on adipocytes via its receptor (OSMR) leads to adipose tissue inflammation and insulin resistance. Our preliminary data indicate that OSM signaling on adipocytes is required for proper adipose tissue function. The mechanisms adipocytes utilize to regulate adipose tissue inflammation in both health and disease remain unclear. We aim to address this knowledge gap by proposing a new regulatory role for the adipocyte. Specifically, we will test the overarching hypothesis that adipocytes tightly regulate free cytokine availability in AT to maintain insulin sensitivity and limit inflammation. Our recent findings are the basis for the specific aims of this proposal. In these aims, we will test the following hypotheses: (1) OSMR-dependent lipolysis is necessary for maintaining energy balance; (2) continued exposure of adipocytes to OSM results in OSMR desensitization, leading to adipocyte insulin resistance; and (3) excess stromal-derived factor 1 and OSM act on macrophages and preadipocytes, respectively, to promote AT inflammation.

Communication between fat cells and immune cells is critical to the normal function of fat tissue. In obesity, the ways fat cells respond to immune cells can change, leading to inflammation and dysfunction in fat tissue. Results of these studies will reveal new cell communication patterns that can be leveraged to treat obesity and other metabolic diseases.