Article

TNF-α induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes†‡

  1. Sandra C. Souza1,*,
  2. Helen J. Palmer1,§,
  3. You-Hou Kang1,¶,
  4. Mia T. Yamamoto1,
  5. Kizito V. Muliro1,
  6. K. Eric Paulson1,2,
  7. Andrew S. Greenberg1,3

Article first published online: 30 JUN 2003

DOI: 10.1002/jcb.10565

Issue

Journal of Cellular Biochemistry

Journal of Cellular Biochemistry

Volume 89, Issue 6, pages 1077–1086, 15 August 2003

Additional Information

How to Cite

Souza, S. C., Palmer, H. J., Kang, Y.-H., Yamamoto, M. T., Muliro, K. V., Eric Paulson, K. and Greenberg, A. S. (2003), TNF-α induction of lipolysis is mediated through activation of the extracellular signal related kinase pathway in 3T3-L1 adipocytes. Journal of Cellular Biochemistry, 89: 1077–1086. doi: 10.1002/jcb.10565

Author Information

  1. 1

    The Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, Massachusetts 02111

  2. 2

    Department of Biochemistry, Tufts University School of Medicine, 136 Harrison Ave., Boston, Massachusetts 02111

  3. 3

    Department of Medicine, New England Medical Center and Tufts University School of Medicine, Box 268, 750 Washington Street, Boston, Massachusetts 02111

  1. §

    Genetics Institute, 200 Cambridge Park Dr., Cambridge, MA 02140.

  2. Department of Medicine, University of Toronto, Toronto, Canada.

*JM-USDA HNRCA at Tufts University, 711 Washington Street, Room 603, Boston, MA 02111.

  1. †

    Data from this manuscript were presented in part at the 58th Annual Meeting of the American Diabetes Association; June, 1998.

  2. ‡

    Sandra C. Souza and Helen J. Palmer contributed equally to the work in this paper.

Publication History

  1. Issue published online: 28 JUL 2003
  2. Article first published online: 30 JUN 2003
  3. Manuscript Accepted: 31 MAR 2003
  4. Manuscript Received: 12 AUG 2002

Funded by

  • The U.S. Department of Agriculture, Agriculture Research Service. Grant Number: 3KO6510
  • NIH. Grant Numbers: P30 DK34928, DK50647
  • American Diabetes Association

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Keywords:

  • perilipin;
  • map kinases;
  • PPARγ

Abstract

Tumor necrosis factor-α (TNF-α) increases adipocyte lipolysis after 6–12 h of incubation. TNF-α has been demonstrated to activate mitogen-activated protein (MAP) kinases including extracellular signal-related kinase (ERK) and N-terminal-c-Jun-kinase (JNK) in different cell types. To determine if the MAP kinases have a role in TNF-α-induced lipolysis, 3T3-L1 adipocytes were treated with the cytokine (10 ng/ml), in the presence or absence of PD98059 or U0126 (100 µM), specific inhibitors of ERK activity. We demonstrated that U0126 or PD98059 blocked TNF-α-induced ERK activity and decreased TNF-α-induced lipolysis by 65 or 76% respectively. The peroxisome-proliferator-activated receptor γ (PPARγ) agonists, rosiglitazone (ros), and 15-deoxy-Δ-12,14- prostaglandin J2 (PGJ2) have been demonstrated to block TNF-α-induced lipolysis. Pretreatment of adipocytes with these agents almost totally blocked TNF-α-induced ERK activation and reduced lipolysis by greater than 90%. TNF-α also stimulated JNK activity, which was not affected by PD98059 or PPARγ agonist treatment. The expression of perilipin, previously proposed to contribute to the mechanism of lipolysis, is diminished in response to TNF-α treatment. Pretreatment of adipocytes with PD98059 or ros significantly blocked the TNF-α-induced reduction of perilipin A protein level as determined by Western analysis. These data suggest that activation of the ERK pathway is an early event in the mechanism of TNF-α-induced lipolysis. © 2003 Wiley-Liss, Inc.

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