Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice

Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice
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DOI:
10.1210/en.2006-0417
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发表时间:
2006-10-01
期刊:
影响因子:
4.8
通讯作者:
Romijn, Johannes A.
Romijn, Johannes A.
中科院分区:
医学2区
文献类型:
--
作者:
den Boer, Marion A. M.;Voshol, Peter J.;Romijn, Johannes A.

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多项研究已表明,在人类中抗炎细胞因子白细胞介素 - 10(IL - 10)的血浆水平或产生能力与胰岛素敏感性之间存在关联。我们研究的目的是探究内源性IL - 10的可利用性在饮食诱导的胰岛素抵抗发展中的保护作用。我们比较了喂食高脂肪饮食6周的IL - 10基因敲除(IL - 10(-/-))小鼠和野生型(wt)小鼠之间的糖脂代谢参数。先前已表明这种饮食会诱导脂肪变性和胰岛素抵抗。高脂肪饮食6周后,在IL - 10(-/-)小鼠和野生型小鼠之间,未观察到体重、基础代谢(通过间接测热法测量)或血浆葡萄糖、甘油三酯或胆固醇水平的差异。然而,在IL - 10(-/-)小鼠中,过夜禁食后血浆游离脂肪酸水平与野生型小鼠相比增加了75%(P < 0.05)。此外,IL - 10(-/-)小鼠肝脏甘油三酯含量增加了54%(P < 0.05)。在高胰岛素 - 正常血糖钳夹试验期间,两组之间在全身或肝脏胰岛素敏感性方面未观察到差异。我们得出结论,在高脂肪饮食期间,基础的IL - 10产生可预防肝脏脂肪变性,但不会提高肝脏或全身的胰岛素敏感性。
Several studies have demonstrated an association in humans between plasma levels or production capacity of the antiinflammatory cytokine IL-10 and insulin sensitivity. The aim of our study was to investigate the protective role of endogenous IL-10 availability in the development of diet-induced insulin resistance. We compared parameters of glucose and lipid metabolism between IL-10(-/-) mice and wild-type (wt) mice fed a high-fat diet for 6 wk. This diet has previously been shown to induce steatosis and insulin resistance. After 6 wk on the high-fat diet, no differences in body weight, basal metabolism ( measured by indirect calorimetry), or plasma levels of glucose, triglycerides, or cholesterol were observed between IL10(-/-) and wt mice. Nonetheless, in IL-10(-/-) mice, plasma free fatty acid levels were 75% increased compared with wt mice after overnight fasting (P < 0.05). In addition, hepatic triglyceride content was 54% increased in IL- 10(-/-) mice ( P < 0.05). During a hyperinsulinemic euglycemic clamp, no differences were observed in whole-body or hepatic insulin sensitivity between both groups. We conclude that basal IL-10 production protects against hepatic steatosis but does not improve hepatic or whole-body insulin sensitivity, during high-fat feeding.