Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-α

Brian N. Finck, Rodney W. Johnson

Research output: Contribution to journalArticlepeer-review


Tumor necrosis factor (TNF)-α stimulates the secretion of the adipocyte-derived hormone leptin. However, the cellular mechanisms by which TNF-α influences leptin production are poorly understood. To examine this issue, epididymal fat pads were isolated from mice and cultured in recombinant murine TNF-α (100 ng/ml). Compared with medium-treated controls, steady-state leptin expression was increased in TNF-α-treated explants. Culture with inhibitors of translation (cycloheximide) or transcription (actinomycin-D) abrogated the induction of leptin following TNF-α. Explants were also cultured in the presence of the anti-inflammatory p38 mitogen-activated protein kinase inhibitor (SB-203580) or PG J2 metabolite [15-deoxy-Δ12,14-PG J2 (PGJ)] and then exposed to TNF-α Both compounds completely abolished TNF-α-induced increases in leptin production. To test the relevance of this in vivo, mice were pretreated with PGJ and then given TNF-α. PGJ treatment markedly blunted the TNF-α-induced increase in leptin, TNF-α, and interleukin-6 gene expression in epididymal adipose tissue. Collectively, these data indicate that TNF-α acutely activates leptin expression and that anti-inflammatory agents can abrogate TNF-α-induced hyperleptinemia.

Original languageEnglish (US)
Pages (from-to)R1429-R1435
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number5 51-5
StatePublished - 2002
Externally publishedYes


  • 15-deoxy-Δ-prostaglandin J
  • Endocrine-immune interaction
  • SB-203580

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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