Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4
Regulation of glucose/lipid metabolism and insulin sensitivity by interleukin-4
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DOI：
10.1038/ijo.2011.168
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发表时间：
2012-07-01
影响因子：
4.9
通讯作者：
Shiau, M-Y
中科院分区：
文献类型：
--
作者：
Chang, Y-H;Ho, K-T;Shiau, M-Y
目的：大量证据表明，长期细胞因子介导的炎症是肥胖和2型糖尿病（T2DM）的危险因素。我们之前的研究揭示了th2来源的细胞因子白介素-4 （IL-4）启动子多态性与T2DM之间的显著相关性，这提示IL-4可能在代谢中起作用。在本研究中，我们重点研究了IL-4对糖脂代谢的调节作用。方法：分别向C57BL/6小鼠腹腔注射含有IL-4全长编码基因（AdIL-4）或重组IL-4的腺病毒，模拟IL-4短暂和长期过表达状态，观察过表达IL-4对糖/脂代谢和胰岛素敏感性的影响。结果：我们的研究结果表明，IL-4通过上调Akt磷酸化而减弱GSK-3 β b活性，从而改善胰岛素敏感性和葡萄糖耐量。IL-4还通过抑制脂肪组织中的脂质积累参与脂质代谢，从而减少体重增加和脂肪量。结论：我们的研究结果提示IL-4通过促进胰岛素敏感性、糖耐量和抑制脂质沉积来调节糖脂代谢。这项研究揭示了IL-4在代谢中的新作用，并为细胞因子/免疫反应、胰岛素敏感性和代谢之间的相互作用提供了新的见解。
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-3 beta b 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.