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Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4

International Journal of Obesity volume 36, pages 993–998 (2012)Cite this article

Abstract

Objective:

Abundant evidence has demonstrated that long-term cytokine-mediated inflammation is a risk factor for obesity and type 2 diabetes mellitus (T2DM). Our previous study reveals a significant association between promoter polymorphisms of Th2-derived cytokine interleukin-4 (IL-4) and T2DM, which suggests possible roles of IL-4 in metabolism. In this study, we focused on examining the putative regulation of glucose and lipid metabolism by IL-4.

Methods:

C57BL/6 mice were intraperitoneally injected with either adenovirus containing full-length IL-4 encoding gene (AdIL-4) or recombinant IL-4 for mimicking the status of transient and long-term IL-4 overexpression, respectively, and the effects of the overexpressed IL-4 to glucose/lipid metabolism and insulin sensitivity were subsequently investigated.

Results:

Our results reveal that IL-4 improves insulin sensitivity and glucose tolerance through upregulating Akt phosphorylation while attenuating GSK-3β activities. IL-4 is also involved in lipid metabolism by inhibiting lipid accumulation in fat tissues, which lead to decreased weight gain and fat mass.

Conclusions:

Our results suggest that IL-4 regulates glucose and lipid metabolism by promoting insulin sensitivity, glucose tolerance and inhibiting lipid deposits. This study uncovers the novel roles of IL-4 in metabolism and provides new insights in the interaction between cytokines/immune responses, insulin sensitivity and metabolism.

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Acknowledgements

This work was supported by National Science Council, Taiwan, Republic of China (NSC97-2320-B-040-006-MY3 and NSC98-2320-B-010-034-MY3). We thank Dr Yuji Nagayama, Department of Pharmacology, Nagasaki University School of Medicine, Japan, and Dr Basil Rapoport, Autoimmune Disease Unit, Cedars-Sinai Research Institute and School of Medicine, University of California, for their gifts of adenovirus in this study.

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Authors and Affiliations

  1. Institute of Biotechnology in Medicine, National Yang-Ming University, Taipei, Taiwan

    Y-H Chang

  2. School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

    Y-H Chang

  3. Department of Life Sciences, National Chung Hsing University, Taichung, Taiwan

    K-T Ho

  4. Institute of Immunology, Chung Shan Medical University, Taichung, Taiwan

    S-H Lu

  5. Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

    C-N Huang

  6. School of Medicine, Chung Shan Medical University, Taichung, Taiwan

    C-N Huang

  7. Hungkuang University, Taichung, Taiwan

    M-Y Shiau

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Correspondence to M-Y Shiau.

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Chang, YH., Ho, KT., Lu, SH. et al. Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4. Int J Obes 36, 993–998 (2012). https://doi.org/10.1038/ijo.2011.168

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