Interplay of pro-and anti-inflammatory cytokines to determine lipid accretion in adipocytes

Y. Wang, H. Wang, V. Hegde, O. Dubuisson, Z. Gao, N. V. Dhurandhar, J. Ye

Research output: Contribution to journalArticle

15 Scopus citations

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.Design: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.

Original languageEnglish
Pages (from-to)1490-1498
Number of pages9
JournalInternational Journal of Obesity
Volume37
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Adiponectin
  • NF-κB
  • PPARg
  • TNF-α
  • mRNA stability
  • transcription

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