Interleukin-15 stimulates adiponectin secretion by 3T3-L1 adipocytes: Evidence for a skeletal muscle-to-fat signaling pathway

Authors

  • LeBris S. Quinn,

    Corresponding author
    1. Geriatric Research, Education, and Clinical Center, 151 American Lake Division, VA Puget Sound Health Care System, Tacoma, WA 98493, USA
    2. Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA
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  • Lena Strait-Bodey,

    1. Research Service, VA Puget Sound Health Care System, Tacoma, WA, USA
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  • Barbara G. Anderson,

    1. Division of Gerontology and Geriatric Medicine, Department of Medicine, University of Washington, Seattle, WA, USA
    2. Research Service, VA Puget Sound Health Care System, Tacoma, WA, USA
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  • Josep M. Argilés,

    1. Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Barcelona, Spain
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  • Peter J. Havel

    1. Department of Nutrition, University of California, Davis, CA, USA
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Corresponding author. 151 American Lake Division, VA Puget Sound Health Care System, Tacoma, WA 98493, USA. Tel.: +1 253 582 8440x76724; fax: +1 253 589 4004. quinnl@u.washington.edu

Abstract

Interleukin-15 (IL-15) is a cytokine which is highly expressed in skeletal muscle tissue, and which has anabolic effects on skeletal muscle protein dynamics both in vivo and in vitro. Additionally, administration of IL-15 to rats and mice inhibits white adipose tissue deposition. To determine if the action of IL-15 on adipose tissue is direct, the capacity of cultured murine 3T3-L1 preadipocytes and adipocytes to respond to IL-15 was examined. IL-15 administration inhibited lipid accumulation in differentiating 3T3-L1 preadipocytes, and stimulated secretion of the adipocyte-specific hormone adiponectin by differentiated 3T3-L1 adipocytes. The latter observation constitutes the first report of a cytokine or growth factor which stimulates adiponectin production. IL-15 mRNA expression by cultured 3T3-L1 adipogenic cells and C2C12 murine skeletal myogenic cells was also examined. Quantitative real-time PCR indicated IL-15 mRNA was expressed by C2C12 skeletal myogenic cells, and was upregulated more than 10-fold in differentiated skeletal myotubes compared to undifferentiated myoblasts. In contrast, 3T3-L1 cells expressed little or no IL-15 mRNA at either the undifferentiated preadipocyte or differentiated adipocyte stages. These findings provide support for the hypothesis that IL-15 functions in a muscle-to-fat endocrine axis which modulates fat:lean body composition and insulin sensitivity.

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