Adipose tissue inflammation directly contributes to the overall inflammatory state in obesity, with leukocytes being major players in the regulation (or dysregulation) of adipocyte function. The pro-inflammatory cytokine, oncostatin M (OSM), is produced by adipose tissue mast cells, macrophages, and T cells. Our recently published data suggest that lack of adipocyte OSM signaling via its receptor (OSMR) leads to adipose tissue inflammation and increased mast cell number. The exact signals involved in this mast cell accumulation remain unknown. We will attempt to address these questions in this proposal. Specifically, we will test the overarching hypothesis that adipocyte OSM signaling is a mediator of adipocyte-leukocyte crosstalk. Our recent findings are the basis for the specific aims of this proposal: (1) Investigate the role of adipocyte OSM-OSMR signaling as a regulator of WAT mast cell proliferation and maturation; and (2) Elucidate the contribution of mast cells to WAT OSM expression and T cell activation. The completion of these aims will help identify the mechanisms by which OSM-OSMR signaling, at the levels of both the adipocyte and the leukocyte, contributes to adipose immune balance. Most importantly, the proposed studies build upon data and experience obtained from my K01 award while representing a new and logical extension of the K01 project. Data generated from these studies will form the basis for future R01 proposals designed to investigate the interactions of the adipose tissue extracellular matrix and immune cells, which is consistent with my long-term research goal.
In obesity, changes in the numbers and types of immune cells found in fat can lead to inflammation. Communication between immune cells and fat cells can cause inflammation but may also be critical to normal tissue function. Results of this study will provide novel insight into how these cells communicate and how we can change their communication patterns to treat obesity and related metabolic diseases.
