title: Anti-inflammatory agents inhibit the induction of leptin by tumor necrosis factor-alpha.
abstract: 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.
authors.affiliation: Department of Animal Sciences, University of Illinois at Urbana-Champaign, 390 Animal Sciences Laboratory, Urbana, Illinois 61801, USA. bfinck@im.wustl.edu
authors.forename: Brian N
authors.initials: BN
authors.lastname: Finck
authors.forename: Rodney W
authors.initials: RW
authors.lastname: Johnson
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D046508:Culture Techniques; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006706:Homeostasis; D007093:Imidazoles / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology; D020738:Leptin / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: C097240:15-deoxy-delta(12,14)-prostaglandin J2; D000893:Anti-Inflammatory Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007093:Imidazoles; D007155:Immunologic Factors; D020738:Leptin; D019384:Nucleic Acid Synthesis Inhibitors; D011500:Protein Synthesis Inhibitors; D011725:Pyridines; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003513:Cycloheximide; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; D015230:Prostaglandin D2