Objective: Adiponectin is an adipocyte-derived hormone that sensitizes insulin and improves energy metabolism in tissues. This study was designed to investigate the direct regulatory effects of adiponectin on lipid metabolism in adipocytes.
Research design and methods: Basal and hormone-stimulated lipolysis were comparatively analyzed using white adipose tissues or primary adipocytes from adiponectin gene knockout and control mice. To further study the underlying mechanisms through which adiponectin suppresses lipolysis, cultured 3T3-L1 adipocytes and adenovirus-mediated gene transduction were used.
Results: Significantly increased lipolysis was observed in both adiponectin gene knockout mice and primary adipocytes from these mice. Hormone-stimulated glycerol release was inhibited in adiponectin-treated adipocytes. Adiponectin suppressed hormone-sensitive lipase activation without altering adipose triglyceride lipase and CGI-58 expression in adipocytes. Moreover, adiponectin reduced protein levels of the type 2 regulatory subunit RIIα of protein kinase A by reducing its protein stability. Ectopic expression of RIIα abolished the inhibitory effects of adiponectin on lipolysis in adipocytes.
Conclusions: This study demonstrates that adiponectin inhibits lipolysis in adipocytes and reveals a novel function of adiponectin in lipid metabolism in adipocytes.