Department of Pharmacology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
Biochimie. 2012 Oct;94(10):2126-30. doi: 10.1016/j.biochi.2012.01.008. Epub 2012 Feb 10.
Adiponectin has been receiving a great deal of attention due to its potential therapeutic use for metabolic and cardiovascular disorders. Adiponectin expression levels and multimerization are down-regulated in obesity and up-regulated by insulin sensitizers such as thiazolidinediones (TZDs), metformin, sulfonylurea and resveratrol (RSV). The precise mechanisms underlying adiponectin up- and down-regulation remain largely unknown, but recent studies indicate that the cellular and plasma levels of adiponectin could be regulated at both transcriptional and post-transcriptional levels. At the post-translational level, TZDs and resveratrol promote adiponectin levels and multimerization via up-regulation of disulfide-bond-A oxidoreductase-like protein (DsbA-L). Adiponectin levels are also stimulated by FOXO1 and AMP-activated protein kinase (AMPK), and are suppressed by PKA or silencing mediator of retinoid and thyroid hormone receptors (SMRT). Since multimerization is important not only for adiponectin function but also for stability, increasing adiponectin multimerization has become a promising drug target for the treatment of metabolic diseases and other related disorders.
脂联素由于其在代谢和心血管疾病方面的潜在治疗用途而受到广泛关注。肥胖症患者的脂联素表达水平和多聚化程度降低，而噻唑烷二酮类（TZD）、二甲双胍、磺酰脲类和白藜芦醇（RSV）等胰岛素增敏剂可上调脂联素。脂联素上调和下调的确切机制仍知之甚少，但最近的研究表明，脂联素的细胞内和血浆水平可以在转录和转录后水平上进行调节。在翻译后水平上，TZD 和白藜芦醇通过上调二硫键 A 氧化还原酶样蛋白（DsbA-L）来促进脂联素水平和多聚化。FOXO1 和 AMP 激活的蛋白激酶（AMPK）也刺激脂联素水平，而蛋白激酶 A 或视黄酸和甲状腺激素受体沉默介体（SMRT）则抑制脂联素水平。由于多聚化不仅对脂联素的功能而且对稳定性很重要，因此增加脂联素的多聚化已成为治疗代谢疾病和其他相关疾病的有前途的药物靶点。
