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. 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.
Ajuwon
Kolapo M
KM
Department of Animal Sciences, Comparative Medicine Program, Purdue University, Lilly Hall of Life Sciences, 915 W State St., West Lafayette, IN 47907-2054, USA.
Spurlock
Michael E
ME
D017667:Adipocytes / Q000378:metabolism*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000502:physiology; D019409:Interleukin-15 / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D008055:Lipids / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D013552:Swine; D013997:Time Factors
D019409:Interleukin-15; D008055:Lipids; D011994:Recombinant Proteins; D011505:Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases