title: Interplay of pro- and anti-inflammatory cytokines to determine lipid accretion in adipocytes.
abstract: OBJECTIVE
  Obesity is associated with an increase in various pro-inflammatory and anti-inflammatory cytokines, but the interplay of these cytokines is incompletely understood. We conducted experiments to test a broader hypothesis that a dynamic interplay of pro-inflammatory and anti-inflammatory cytokines controls lipid storage in adipocytes.
  
  
  METHODS
  Three experiments were designed to test the overall hypothesis that proinflammatory cytokine (for example, tumor necrosis factor-α (TNF-α) inhibits anti-inflammatory cytokine (for example, adiponectin) activity in an attempt to limit excess lipid accumulation in adipocytes.
  
  
  RESULTS
  Experiment one showed that in pro-inflammatory animal models (ap2-P65, ob/ob and high-fat diet-induced obese mice), the increase in TNF-α expression was associated with a decrease in adiponectin expression. Experiment two showed that in 3T3-L1 adipocytes, TNF-α significantly reduced lipid accumulation and glucose uptake induced by adiponectin, and increased lipolysis. Experiment three showed that in 3T3-L1 adipocytes, TNF-α reduced mRNA and protein expression of adiponectin. Adiponectin gene transcription and mRNA stability were both reduced by TNF-α. The expression of peroxisome proliferator-activated receptor gamma, an activator of adiponectin gene promoter, was reduced by TNF-α. The inhibitory activity of TNF-α was blocked by the chemical inhibitors of NF-κB and super suppressor IκBα.
  
  
  CONCLUSIONS
  TNF-α opposes the action of adiponectin in the regulation of lipid metabolism, and inhibits adiponectin expression at transcriptional and post-transcriptional levels. The results suggest that pro-inflammatory cytokine inhibit anti-inflammatory cytokine in adipocytes to reduce lipid storage. This suggests a potential role of anti-inflammatory cytokines in the control of adipose tissue expansion.
authors: Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.
authors: Y
authors: Y
authors: Wang
authors: H
authors: H
authors: Wang
authors: V
authors: V
authors: Hegde
authors: O
authors: O
authors: Dubuisson
authors: Z
authors: Z
authors: Gao
authors: N V
authors: NV
authors: Dhurandhar
authors: J
authors: J
authors: Ye
mesh_terms: D041721:3T3-L1 Cells / Q000378:metabolism; D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015153:Blotting, Western; D005260:Female; D005786:Gene Expression Regulation; D007249:Inflammation / Q000378:metabolism*; D007333:Insulin Resistance; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D008822:Mice, Transgenic; D009765:Obesity / Q000378:metabolism* / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D052242:Adiponectin; D014409:Tumor Necrosis Factor-alpha
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