Figure 9. Schematic Diagram of Proposed Pathophysiological Role of Adipocyte-Derived A-SAA in Human Obesity.

A-SAA secreted from adipocytes acts locally on adipose SVCs to stimulate cytokine release and in adipocytes to stimulate lipolysis, increasing FFA release and decreasing insulin sensitivity in adipocytes, and possibly contributing to systemic dyslipidemia. In addition, A-SAA secretion by adipocytes into the circulation stimulates cytokine production at more distant sites, including in endothelial cells and monocytes, resulting in endothelial dysfunction, monocyte infiltration, accelerated atherosclerosis, and possibly insulin resistance in muscle and liver. A-SAA-stimulated lipolysis increases circulating FFA concentrations, further contributing to insulin resistance in muscle and liver. Finally, A-SAA incorporation into HDL accelerates its degradation and impairs its function, resulting in decreased HDL and accelerated atherosclerosis.