Direct regulation of lipolysis by interleukin-15 in primary pig adipocytes

We recently provided evidence that interleukin-15 (IL-15) is expressed lowly in the pig adipocyte and that interferon-gamma (IFN-gamma) markedly increases this expression through a pathway regulated in part by protein kinase C (Ajuwon KM, Jacobi SK, Kuske JL, and Spurlock ME. Am J Physiol Regul Integr Comp Physiol 286: R547 - R553, 2004). In the present study, we tested the hypothesis that IL-15 acts directly on the adipocyte to regulate lipid accretion by enhancing lipolysis or suppressing lipogenesis. Using recombinant porcine IL-15, we determined that this cytokine stimulates lipolysis in a dose-dependent manner ( P < 0.001). Furthermore, comparative studies with other cytokines showed that IL-15 is more potent in its acute stimulation of lipolysis than either TNF-alpha, IL-6, or LPS ( P < 0.001). When specific inhibitors of protein kinase A or Janus kinase are present, the lipolytic effect of IL-15 is attenuated ( P < 0.01). These data indicate that, in addition to its regulation of muscle protein accretion and T-cell growth and development, IL-15 also targets the adipocyte directly to alter stimulate lipolysis. Thus, when induced by IFN-gamma or other inflammatory mediators, IL-15 may be a significant homeorhetic factor that mobilizes and directs energy away from the adipocyte to other cells during the acute phase of the inflammatory response.