Journal
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY
Volume 282, Issue 5, Pages R1429-R1435Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpregu.00569.2001
Keywords
endocrine-immune interaction; 15-deoxy-Delta(12,14) prostaglandin J(2); SB-203580
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Funding
- NIDDK NIH HHS [DK49311, DK51576] Funding Source: Medline
- NIGMS NIH HHS [GM007143] Funding Source: Medline
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Tumor necrosis factor (TNF)-alpha stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-alpha influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-alpha (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-alpha-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-alpha. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J(2) metabolite [15-deoxy-Delta(12,14)-PG J(2) (PGJ)] and then exposed to TNF-alpha. Both compounds completely abolished TNF-alpha-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-alpha. PGJ treatment markedly blunted the TNF-alpha-induced increase in leptin, TNF-alpha, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-alpha acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-alpha-induced hyperleptinemia.
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