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Int J Obes (Lond). 2013 Nov;37(11):1490-8. doi: 10.1038/ijo.2013.9. Epub 2013 Feb 5.

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

Author information

1
Antioxidant and Gene Regulation Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA.

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.

PMID:
23381555
PMCID:
PMC3657600
DOI:
10.1038/ijo.2013.9
[Indexed for MEDLINE]
Free PMC Article

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