Ukkola Olavi, Santaniemi Merja
Department of Internal Medicine and Biocenter Oulu, University of Oulu, Kajaanintie 50/P.O. Box 5000, 90220 Oulu, Finland.
J Mol Med (Berl). 2002 Nov;80(11):696-702. doi: 10.1007/s00109-002-0378-7. Epub 2002 Sep 10.
Adiponectin is a novel polypeptide that is highly specific to adipose tissue. In contrast to other adipocytokines, adiponectin levels are decreased in obesity and associated comorbidities, such as type 2 diabetes. Decreased expression of adiponectin is correlated with insulin resistance. It has been suggested that several agents, such as tumor necrosis factor alpha, could mediate their effects on insulin metabolism through modulating adiponectin secretion from adipocytes. The mechanisms for the development of atherosclerotic vascular disease in obese individuals are largely unknown. Several findings support the interesting hypothesis that adiponectin could be a link between obesity and related atherosclerosis. First, adiponectin levels are lower in patients with coronary artery disease. Second, adiponectin modulates endothelial function and has an inhibitory effect on vascular smooth muscle cell proliferation. Moreover, adiponectin is accumulated more preferably to the injured vascular wall than intact vessels and has been shown to suppress macrophage-to-foam cell transformation. Adiponectin may also be involved in the modulation of inflammation. Thiazolidinediones, antiatherogenic and other effects have been explained by their direct enhancing effect on adiponectin. In conclusion, adiponectin has anti-inflammatory and antiatherogeneic effects as well as multiple beneficial effects on metabolism. Therefore it is not a surprise that adiponectin therapy has been tested in animal models of obesity, and it has been shown to ameliorate hyperglycemia and hyperinsulinemia without inducing weight gain or even inducing weight loss in some studies. Unlike agents that exert their effects centrally, adiponectin's effects seem to be peripherally mediated. The evidence of an association between adiponectin and the metabolic and cardiovascular complications of obesity is growing all the time.
脂联素是一种对脂肪组织具有高度特异性的新型多肽。与其他脂肪细胞因子不同,肥胖及相关合并症(如2型糖尿病)患者的脂联素水平会降低。脂联素表达降低与胰岛素抵抗相关。有研究表明,几种因子,如肿瘤坏死因子α,可通过调节脂肪细胞分泌脂联素,来介导其对胰岛素代谢的影响。肥胖个体发生动脉粥样硬化性血管疾病的机制在很大程度上尚不清楚。多项研究结果支持了一个有趣的假说,即脂联素可能是肥胖与相关动脉粥样硬化之间的联系。首先,冠心病患者的脂联素水平较低。其次,脂联素可调节内皮功能,并对血管平滑肌细胞增殖具有抑制作用。此外,与完整血管相比,脂联素更倾向于在受损血管壁处蓄积,并且已被证明可抑制巨噬细胞向泡沫细胞的转化。脂联素也可能参与炎症调节。噻唑烷二酮类药物的抗动脉粥样硬化及其他作用,已通过其对脂联素的直接增强作用得到解释。总之,脂联素具有抗炎和抗动脉粥样硬化作用,以及对代谢的多种有益作用。因此,在肥胖动物模型中测试脂联素治疗并不奇怪,并且在一些研究中已表明,它可改善高血糖和高胰岛素血症,而不会导致体重增加,甚至在某些情况下还会导致体重减轻。与作用于中枢的药物不同,脂联素的作用似乎是由外周介导的。脂联素与肥胖的代谢和心血管并发症之间存在关联的证据一直在增加。