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Research Article Free access | 10.1172/JCI119824

Tumor necrosis factor-alpha contributes to obesity-related hyperleptinemia by regulating leptin release from adipocytes.

T G Kirchgessner, K T Uysal, S M Wiesbrock, M W Marino, and G S Hotamisligil

Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.

Find articles by Kirchgessner, T. in: PubMed | Google Scholar

Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.

Find articles by Uysal, K. in: PubMed | Google Scholar

Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.

Find articles by Wiesbrock, S. in: PubMed | Google Scholar

Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.

Find articles by Marino, M. in: PubMed | Google Scholar

Bristol-Myers Squibb Co., Pharmaceutical Research Institute, Princeton, New Jersey 08543, USA.

Find articles by Hotamisligil, G. in: PubMed | Google Scholar

Published December 1, 1997 - More info

Published in Volume 100, Issue 11 on December 1, 1997
J Clin Invest. 1997;100(11):2777–2782. https://doi.org/10.1172/JCI119824.
© 1997 The American Society for Clinical Investigation
Published December 1, 1997 - Version history
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Abstract

Cytokines, in particular tumor necrosis factor-alpha (TNF-alpha), have significant effects on energy metabolism and appetite although their mechanisms of action are largely unknown. Here, we examined whether TNF-alpha modulates the production of leptin, the recently identified fat-specific energy balance hormone, in cultured adipocytes and in mice. TNF-alpha treatment of 3T3-L1 adipocytes resulted in rapid stimulation of leptin accumulation in the media, with a maximum effect at 6 h. This stimulation was insensitive to cycloheximide, a protein synthesis inhibitor, but was completely inhibited by the secretion inhibitor brefeldin A, indicating a posttranslational effect. Treatment of mice with TNF-alpha also caused a similar increase in plasma leptin levels. Finally, in obese TNF-alpha-deficient mice, circulating leptin levels were significantly lower, whereas adipose tissue leptin was higher compared with obese wild-type animals. These data provide evidence that TNF-alpha can act directly on adipocytes to regulate the release of a preformed pool of leptin. Furthermore, they suggest that the elevated adipose tissue expression of TNF-alpha that occurs in obesity may contribute to obesity-related hyperleptinemia.

Version history
  • Version 1 (December 1, 1997): No description

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