Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction.
Adiponectin, a Therapeutic Target for Obesity, Diabetes, and Endothelial Dysfunction.
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DOI：
10.3390/ijms18061321
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发表时间：
2017-06-21
影响因子：
5.6
通讯作者：
Jain SK
中科院分区：
文献类型：
--
作者：
Achari AE;Jain SK
脂联素（Adiponectin）是脂肪细胞分泌的最丰富的多肽，其减少在肥胖相关疾病中起着重要作用，包括胰岛素抵抗/2型糖尿病和心血管疾病。除了脂肪细胞，其他细胞类型，如骨骼肌和心肌细胞和内皮细胞，也可以产生这种脂肪细胞因子。脂联素效应由脂联素受体介导，脂联素受体以两种亚型（AdipoR 1和AdipoR 2）存在。脂联素直接作用于肝脏、骨骼肌和血管系统，在循环系统中以多聚体形式存在。近年来发现，内质网ER相关蛋白包括ER氧化还原酶1-α（Ero 1-α）、ER驻留蛋白44（ERp 44）、二硫键A氧化还原酶样蛋白（DsbA-L）和葡萄糖调节蛋白94（GPR 94）等，参与脂联素高级复合物的组装和分泌。最近的数据表明，高分子量（HMW）复合物在代谢组织中具有主导作用。研究表明，在人类和啮齿类动物中给予脂联素具有胰岛素增敏、抗动脉粥样硬化和抗炎作用，并且在某些情况下，还可以减轻体重。因此，人类的脂联素替代疗法可能是治疗肥胖、胰岛素抵抗/2型糖尿病和动脉粥样硬化的潜在多功能治疗靶点。本文就脂联素在肥胖、胰岛素抵抗和心血管疾病中的作用及调节机制作一综述。
Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review.