Role of the fatty acid binding protein mal1 in obesity and insulin resistance
Role of the fatty acid binding protein mal1 in obesity and insulin resistance
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DOI：
10.2337/diabetes.52.2.300
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发表时间：
2003-02-01
期刊：
影响因子：
7.7
通讯作者：
Hotamisligil, GS
中科院分区：
文献类型：
--
作者：
Maeda, K;Uysal, KT;Hotamisligil, GS
代谢综合征是一组代谢和炎症异常，包括肥胖、胰岛素抵抗、2型糖尿病、高血压、血脂异常和动脉粥样硬化。脂肪酸结合蛋白aP 2（fatty acid binding protein [FABP]-4）和mall（FABP 5）密切相关，并且两者都在脂肪细胞中表达。先前在aP 2缺陷小鼠中的研究已经表明aP 2在肥胖相关的胰岛素抵抗、2型糖尿病和动脉粥样硬化中的重要作用。然而，小分子的生物学功能尚不清楚。在这里，我们报告了在mall基因中具有靶向无效突变的小鼠以及从aP 2启动子/增强子过表达mall的转基因小鼠的产生，以解决在存在或不存在肥胖的情况下该FABP在代谢调节中的作用。为了解决第二脂肪细胞FABP在肥胖存在和缺乏的代谢调节中的作用，在肥胖和胰岛素抵抗的两种模型中，缺乏mall导致全身胰岛素敏感性增加。从Mall缺陷小鼠分离的脂肪细胞也表现出增强的胰岛素刺激的葡萄糖转运能力。相比之下，在脂肪组织中表达高水平mall的小鼠显示降低的全身胰岛素敏感性。因此，我们的研究结果表明，小调节脂肪组织的功能，并有助于全身葡萄糖代谢，并构成一个潜在的治疗靶点在胰岛素抵抗。
The metabolic syndrome is a cluster of metabolic and inflammatory abnormalities including obesity, insulin resistance, type 2 diabetes, hypertension, dyslipidemia, and atherosclerosis. The fatty acid binding proteins aP2 (fatty acid binding protein [FABP]-4) and mall (FABP5) are closely related and both are expressed in adipocytes. Previous studies in aP2-deficient mice have indicated a significant role for aP2 in obesity-related insulin resistance, type 2 diabetes, and atherosclerosis. However, the biological functions of mall are not known. Here, we report the generation of mice with targeted null mutations in the mall gene as well as transgenic mice overexpressing mall from the aP2 promoter/enhancer to address the role of this FABP in metabolic regulation in the presence or absence of obesity. To address the role of the second adipocyte FABP in metabolic regulation in the presence and deficiency of obesity, absence of mall resulted in increased systemic insulin sensitivity in two models of obesity and insulin resistance. Adipocytes isolated from mall-deficient mice also exhibited enhanced insulin-stimulated glucose transport capacity. In contrast, mice expressing high levels of mall in adipose tissue display reduced systemic insulin sensitivity. Hence, our results demonstrate that mall modulates adipose tissue function and contributes to systemic glucose metabolism and constitutes a potential therapeutic target in insulin resistance.