Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice
Voluntary exercise improves insulin sensitivity and adipose tissue inflammation in diet-induced obese mice
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DOI：
10.1152/ajpendo.00309.2007
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发表时间：
2008-09-01
影响因子：
5.1
通讯作者：
Maratos-Flier, Eleftheria
中科院分区：
文献类型：
--
作者：
Bradley, Richard L.;Jeon, Justin Y.;Maratos-Flier, Eleftheria
锻炼促进体重减轻，提高胰岛素敏感性。然而，其有益作用的分子机制尚不完全清楚。肥胖与炎性细胞因子的产生增加相关，而炎性细胞因子的产生反过来又导致系统性胰岛素抵抗。为了验证运动减轻这种炎症反应从而改善胰岛素敏感性的假设，我们开发了一个自愿运动的模型，通过喂食高脂肪/高蔗糖饮食(HFD)使小鼠肥胖。4wk后，饲喂饲料的小鼠体重增加2.3+/-0.3g，高脂饲料喂养的小鼠体重增加6.8+/-0.5g，4wk后，将小鼠分为4组：不运动组、运动组，再监测6周。Chow-no运动组和HFD-no运动组小鼠的体重分别增加了1.2+/-0.3 g和3.3+/-0.5 g。运动小鼠的食物消耗量更高，但不会增加额外的体重。正如预期的那样，GTT和ITT显示HFD-no运动小鼠的糖耐量和胰岛素抵抗受损。然而，糖耐量显著改善，胰岛素敏感性在高脂运动动物中完全正常化。此外，HFD小鼠脂肪组织中肿瘤坏死因子-α、单核细胞趋化蛋白-1、纤溶酶原激活物-1和IKK-β的表达均高于正常对照组，而运动可逆转这些炎性细胞因子的表达。相反，这些细胞因子在肝脏中的表达在四组中没有变化。这些结果表明，运动部分地降低了肥胖小鼠的肥胖度，逆转了胰岛素抵抗，并减少了脂肪组织的炎症，尽管继续摄入高脂饮食。
Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production of inflammatory cytokines, which in turn, contributes to systemic insulin resistance. To test the hypothesis that exercise mitigates this inflammatory response, thereby improving insulin sensitivity, we developed a model of voluntary exercise in mice made obese by feeding of a high fat/high sucrose diet (HFD). Over four wk, mice fed chow gained 2.3 +/- 0.3 g, while HFD mice gained 6.8 +/- 0.5 g. After 4 wk, mice were subdivided into four groups: chow-no exercise, chow-exercise, HFD-no exercise, HFD-exercise and monitored for an additional 6 wk. Chow-no exercise and HFD-no exercise mice gained an additional 1.2 +/- 0.3 g and 3.3 +/- 0.5 g respectively. Exercising mice had higher food consumption, but did not gain additional weight. As expected, GTT and ITT showed impaired glucose tolerance and insulin resistance in HFD-no exercise mice. However, glucose tolerance improved significantly and insulin sensitivity was completely normalized in HFD-exercise animals. Furthermore, expression of TNF-alpha, MCP-1, PAI-1 and IKK beta was increased in adipose tissue from HFD mice compared with chow mice, whereas exercise reversed the increased expression of these inflammatory cytokines. In contrast, expression of these cytokines in liver was unchanged among the four groups. These results suggest that exercise partially reduces adiposity, reverses insulin resistance and decreases adipose tissue inflammation in diet-induced obese mice, despite continued consumption of HFD.