Whitehead J P, Richards A A, Hickman I J, Macdonald G A, Prins J B
Centre for Diabetes and Endocrine Research, University of Queensland, Princess Alexandra Hospital, Brisbane, Australia.
Diabetes Obes Metab. 2006 May;8(3):264-80. doi: 10.1111/j.1463-1326.2005.00510.x.
Adiponectin is a recently described adipokine that has been recognized as a key regulator of insulin sensitivity and tissue inflammation. It is produced by adipose tissue (white and brown) and circulates in the blood at very high concentrations. It has direct actions in liver, skeletal muscle and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation [via up-regulation of adenosine monophosphate-activated protein kinase (AMPK) activity] and decrease vascular inflammation. Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in the liver. In contrast to other adipokines, adiponectin secretion and circulating levels are inversely proportional to body fat content. Levels are further reduced in subjects with diabetes and coronary artery disease. Adiponectin antagonizes many effects of tumour necrosis factor-alpha(TNF-alpha) and this, in turn, suppresses adiponectin production. Furthermore, adiponectin secretion from adipocytes is enhanced by thiazolidinediones (which also act to antagonize TNF-alpha effects). Thus, adiponectin may be the common mechanism by which TNF-alpha promotes, and the thiazolidinediones suppress, insulin resistance and inflammation. Two adiponectin receptors, termed AdipoR1 and AdipoR2, have been identified and these are ubiquitously expressed. AdipoR1 is most highly expressed in skeletal muscle and has a prominent action to activate AMPK, and hence promote lipid oxidation. AdipoR2 is most highly expressed in liver, where it enhances insulin sensitivity and reduces steatosis via activation of AMPK and increased peroxisome-proliferator-activated receptor alpha ligand activity. T-cadherin, which is expressed in endothelium and smooth muscle, has been identified as an adiponectin-binding protein with preference for HMW adiponectin multimers. Given the low levels of adiponectin in subjects with the metabolic syndrome, and the beneficial effect of the adipokine in animal studies, there is exciting potential for adiponectin replacement therapy in insulin resistance and related disorders.
脂联素是一种最近被描述的脂肪因子，已被公认为胰岛素敏感性和组织炎症的关键调节因子。它由脂肪组织（白色和棕色）产生，并以非常高的浓度在血液中循环。它在肝脏、骨骼肌和血管系统中具有直接作用，在改善肝脏胰岛素敏感性、增加燃料氧化[通过上调腺苷单磷酸激活蛋白激酶（AMPK）活性]和减少血管炎症方面发挥着重要作用。脂联素以不同分子量形式存在于循环中，由多聚化产生。最近的数据表明，高分子量（HMW）复合物在肝脏中具有主要作用。与其他脂肪因子不同，脂联素的分泌和循环水平与体脂含量成反比。糖尿病和冠心病患者的脂联素水平进一步降低。脂联素拮抗肿瘤坏死因子-α（TNF-α）的许多作用，而这反过来又抑制脂联素的产生。此外，噻唑烷二酮类药物可增强脂肪细胞分泌脂联素（其也起到拮抗TNF-α作用）。因此，脂联素可能是TNF-α促进以及噻唑烷二酮类药物抑制胰岛素抵抗和炎症的共同机制。已鉴定出两种脂联素受体，称为AdipoR1和AdipoR2，它们在全身广泛表达。AdipoR1在骨骼肌中表达最高，具有激活AMPK的显著作用，从而促进脂质氧化。AdipoR2在肝脏中表达最高，通过激活AMPK和增加过氧化物酶体增殖物激活受体α配体活性来增强胰岛素敏感性并减少脂肪变性。在内皮和平滑肌中表达的T-钙黏蛋白已被鉴定为一种脂联素结合蛋白，对HMW脂联素多聚体具有偏好性。鉴于代谢综合征患者脂联素水平较低，且该脂肪因子在动物研究中具有有益作用，脂联素替代疗法在胰岛素抵抗及相关疾病中具有令人兴奋的潜力。
