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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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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DOI: https://doi.org/10.1038/ijo.2011.168
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