title: IGF-I attenuates FFA-induced activation of JNK1 phosphorylation and TNFα expression in human subcutaneous preadipocytes.
abstract: OBJECTIVE
  Free fatty acids (FFAs) are increased in visceral fat and contribute to insulin resistance through multiple mechanisms, including c-Jun N-terminal kinase (JNK) activation and expression of TNFα. Given that insulin-like growth factor-1 (IGF-1)-mediated proliferation is impaired in omental compared to subcutaneous (SC) preadipocytes, we investigated IGF-I anti-inflammatory action in preadipocytes from SC and omental adipose tissue.
  
  
  METHODS
  Preadipocytes isolated from abdominal SC and omental fat of obese subjects were studied in primary culture. Cells were exposed to FFAs with or without IGF-I pretreatment followed by analysis of cytokine expression and JNK phosphorylation. Lentivirus infection was used to express a constitutively active AKT (myr-AKT) in omental preadipocytes.
  
  
  RESULTS
  FFAs increased the expression of tumor necrosis factor (TNF)α, interleukin (IL)-6, and monocyte chemotactic protein (MCP)-1 in SC and omental preadipocytes. IGF-I pretreatment reduced FFA-induced JNK1 phosphorylation and TNFα expression in SC but not omental preadipocytes. Treatment with the JNK1/2 inhibitor SP600125 reduced FFA-induced expression of TNFα. FFAs and MALP-2, a specific TLR2/6 ligand, but not specific ligands for TLR4 and TLR1/2, increased JNK1 phosphorylation. IGF-I completely inhibited MALP-2-stimulated phosphorylation of JNK1. Expression of myr-AKT in omental preadipocytes inhibited FFA-stimulated JNK1 phosphorylation.
  
  
  CONCLUSIONS
  IGF-I attenuated FFA-induced JNK1 phosphorylation and TNFα expression through activation of AKT in human subcutaneous but not omental preadipocytes.
authors.affiliation: Department of Pediatrics, Rhode Island Hospital and Warren Alpert Medical School of Brown University, Providence, Rhode Island, USA.
authors.forename: Otilia
authors.initials: O
authors.lastname: Neacsu
authors.forename: Kelly
authors.initials: K
authors.lastname: Cleveland
authors.forename: Haiyan
authors.initials: H
authors.lastname: Xu
authors.forename: Tamara T
authors.initials: TT
authors.lastname: Tchkonia
authors.forename: James L
authors.initials: JL
authors.lastname: Kirkland
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Boney
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000328:Adult; D000873:Anthracenes / Q000494:pharmacology; D050218:Body Fat Distribution; D005230:Fatty Acids, Nonesterified / Q000378:metabolism* / Q000494:pharmacology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D007333:Insulin Resistance; D007334:Insulin-Like Growth Factor I / Q000378:metabolism* / Q000494:pharmacology; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D055666:Lipopeptides / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000378:metabolism; D009852:Omentum; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D050507:Subcutaneous Fat, Abdominal / Q000187:drug effects / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D005230:Fatty Acids, Nonesterified; D018836:Inflammation Mediators; D055666:Lipopeptides; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D007334:Insulin-Like Growth Factor I; C106335:macrophage stimulatory lipopeptide 2; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases