Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines
Chronic ethanol-induced insulin resistance is associated with macrophage infiltration into adipose tissue and altered expression of adipocytokines
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DOI：
10.1111/j.1530-0277.2007.00452.x
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发表时间：
2007-09-01
影响因子：
3.2
通讯作者：
Nagy, Laura E.
中科院分区：
文献类型：
--
作者：
Kang, Li;Sebastian, Becky M.;Nagy, Laura E.
背景：长期饮酒会破坏葡萄糖稳态，并与胰岛素抵抗的发生有关。虽然脂肪组织和骨骼肌是两个主要的器官，利用葡萄糖响应胰岛素，这两个组织的相对贡献受损的葡萄糖稳态在慢性乙醇喂养是未知的。由于胰岛素抵抗的其他模型，如肥胖，其特征在于巨噬细胞浸润到脂肪组织中，以及在调节胰岛素敏感性中起核心作用的脂肪细胞因子表达的变化，我们假设慢性乙醇诱导的胰岛素抵抗与巨噬细胞浸润到脂肪组织中的增加和脂肪组织脂肪细胞因子表达的变化有关。方法：雄性Wistar大鼠喂以含酒精的液体饲料作为36%的热量或配对喂养对照饮食4周。采用高胰岛素-正葡萄糖钳夹技术结合同位素示踪剂研究了长期乙醇喂养对胰岛素刺激的葡萄糖利用的影响。此外，巨噬细胞浸润到脂肪组织和脂肪细胞因子的表达也进行了评估后，慢性乙醇喂养。结果如下：高胰岛素-正葡萄糖钳夹研究表明，长期乙醇喂养大鼠降低全身葡萄糖利用率，降低胰岛素介导的肝葡萄糖产生抑制。在高胰岛素-正葡萄糖钳夹过程中，慢性乙醇喂养降低了附睾、皮下和网膜脂肪组织的葡萄糖摄取，但对骨骼肌的葡萄糖处理没有影响。慢性乙醇喂养增加了巨噬细胞向附睾脂肪组织的浸润，并改变了脂肪细胞因子的mRNA表达：单核细胞趋化蛋白1、肿瘤坏死因子α和白细胞介素-6的mRNA表达增加，而视黄醇结合蛋白4和脂联素的mRNA表达在附睾脂肪组织中减少。结论：这些数据表明，长期乙醇喂养导致胰岛素抵抗的发展，与受损的胰岛素介导的肝葡萄糖产生的抑制和减少胰岛素刺激的葡萄糖摄取到脂肪组织。慢性乙醇诱导的胰岛素抵抗与脂肪组织中巨噬细胞浸润增加以及脂肪组织脂肪细胞因子表达的变化有关。
Background: Chronic ethanol consumption disrupts glucose homeostasis and is associated with the development of insulin resistance. While adipose tissue and skeletal muscle are the two major organs utilizing glucose in response to insulin, the relative contribution of these two tissues to impaired glucose homeostasis during chronic ethanol feeding is not known. As other models of insulin resistance, such as obesity, are characterized by an infiltration of macrophages into adipose tissue, as well as changes in the expression of adipocytokines that play a central role in the regulation of insulin sensitivity, we hypothesized that chronic ethanol-induced insulin resistance would be associated with increased macrophage infiltration into adipose tissue and changes in the expression of adipocytokines by adipose tissue. Methods: Male Wistar rats were fed a liquid diet containing ethanol as 36% of calories or pair-fed a control diet for 4 weeks. The effects of chronic ethanol feeding on insulin-stimulated glucose utilization were studied using the hyperinsulinemic-euglycemic clamp technique, coupled with the use of isotopic tracers. Further, macrophage infiltration into adipose tissue and expression of adipocytokines were also assessed after chronic ethanol feeding. Results: Hyperinsulinemic-euglycemic clamp studies revealed that chronic ethanol feeding to rats decreased whole-body glucose utilization and decreased insulin-mediated suppression of hepatic glucose production. Chronic ethanol feeding decreased glucose uptake in epididymal, subcutaneous, and omental adipose tissue during the hyperinsulinemic-euglycemic clamp, but had no effect on glucose disposal in skeletal muscle. Chronic ethanol feeding increased the infiltration of macrophages into epididymal adipose tissue and changed the expression of mRNA for adipocytokines: expression of mRNA for monocyte chemoattractant protein 1, tumor necrosis factor alpha, and interleukin-6 were increased, while expression of mRNA for retinol binding protein 4 and adiponectin were decreased in epididymal adipose tissue. Conclusions: These data demonstrate that chronic ethanol feeding results in the development of insulin resistance, associated with impaired insulin-mediated suppression of hepatic glucose production and decreased insulin-stimulated glucose uptake into adipose tissue. Chronic ethanol-induced insulin resistance was associated with increased macrophage infiltration into adipose tissue, as well as changes in the expression of adipocytokines by adipose tissue.