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Adipocyte and Cell Biology

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

International Journal of Obesity volume 37, pages 1490–1498 (2013)Cite this article

Subjects

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.

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Acknowledgements

We appreciate the technical support from Ms Xin Ye. Quantitative real-time PCR assay was conducted in the genomics core of the Pennington Biomedical Research Center. The core is supported by the NIH grants (P30DK072476 and P20 GM103528). This work was supported by the National Institute of Health research projects (DK085495; DK068036) to Ye, J.

Author contributions

YW, HW, VH and OD, performed the experiments. VH, NVD, GZ and JY analyzed the data and wrote the manuscript. JY is fully responsible for this article. All authors read and approved the final manuscript.

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Author notes

  1. Y Wang and H Wang: These authors contributed equally to this study.

Authors and Affiliations

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

    Y Wang, Z Gao & J Ye

  2. Research Center for Immunology, Xinxiang Medical University, Xinxiang, Henan Province, China

    H Wang

  3. Infection and Obesity Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA, USA

    V Hegde, O Dubuisson & N V Dhurandhar

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  1. Y Wang
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Correspondence to J Ye.

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Wang, Y., Wang, H., Hegde, V. et al. Interplay of pro- and anti-inflammatory cytokines to determine lipid accretion in adipocytes. Int J Obes 37, 1490–1498 (2013). https://doi.org/10.1038/ijo.2013.9

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