title: NFκB as a potent regulator of inflammation in human adipose tissue, influenced by depot, adiposity, T2DM status, and TNFα.
abstract: OBJECTIVE
  Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk.
  
  
  METHODS
  This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques.
  
  
  RESULTS
  Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NFκB (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNFα treated AbdSc adipocytes increased NFκB activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NFκB as a modulator of TNFα secretion.
  
  
  CONCLUSIONS
  These studies suggest distinct changes in NFκB and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNFα leading to activation of NFκB. Consequently NFκB appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NFκB as a potential key target for therapeutic intervention.
authors: Division of Metabolic and Vascular Health, Warwick Medical School, University of Warwick, Coventry, UK.
authors: Alison L
authors: AL
authors: Harte
authors: Gyanendra
authors: G
authors: Tripathi
authors: Milan K
authors: MK
authors: Piya
authors: Thomas M
authors: TM
authors: Barber
authors: John C
authors: JC
authors: Clapham
authors: Nasser
authors: N
authors: Al-Daghri
authors: Dara
authors: D
authors: Al-Disi
authors: Warunee
authors: W
authors: Kumsaiyai
authors: Ponnusamy
authors: P
authors: Saravanan
authors: Anne E
authors: AE
authors: Fowler
authors: Joseph P
authors: JP
authors: O'Hare
authors: Sudhesh
authors: S
authors: Kumar
authors: Philip G
authors: PG
authors: McTernan
mesh_terms: D000273:Adipose Tissue / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D050154:Adiposity / Q000502:physiology*; D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology*; D015434:Panniculitis / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*
chemical_list: D016328:NF-kappa B; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8