Department of Chemistry and Biochemistry, University of Arizona, MRB Diabetes Research, P.O. Box 245218, Tucson, AZ, 85724, USA,
Rev Endocr Metab Disord. 2014 Jun;15(2):125-36. doi: 10.1007/s11154-013-9256-6.
Adiponectin is among the most studied adipokines, the collection of molecules secreted from adipose tissue. It is also one of the most architecturally complex adipokines with its various oligomeric states that include trimers, hexamers, nonamers (9mers), dodecamers (12mers), and octadecamers (18mers). The importance of adiponectin in metabolic regulation is underscored by its strong positive associations with improvement in insulin action and also decreased risks for developing type 2 diabetes. Understanding the mechanisms involved in maintaining the steady-state concentrations of adiponectin oligomers in circulation is therefore likely to provide important insight into the development of insulin resistance. This review will discuss the current state of knowledge regarding the biochemical composition of adiponectin oligomers, the commonly used techniques to analyze them, and the known post-translational modifications that affect their assembly. Evidence based on in vitro oligomer assembly reactions in support of a "cystine ratchet" model of adiponectin oligomer formation will be considered along with limitations of the evidence. Secretory pathway proteins that have been shown to affect the distribution of adiponectin oligomers will also be discussed along with hypotheses regarding their potential involvement in the cystine ratchet model of adiponectin oligomerization.
脂联素是研究最多的脂肪因子之一，这些分子是从脂肪组织中分泌出来的。它也是结构最复杂的脂肪因子之一，具有多种寡聚状态，包括三聚体、六聚体、九聚体（9 mer）、十二聚体（12mer）和十八聚体（18mer）。脂联素在代谢调节中的重要性，突出表现在它与胰岛素作用的改善呈强烈正相关，也与 2 型糖尿病发病风险降低有关。因此，了解维持循环中脂联素寡聚体稳态浓度的机制，很可能为胰岛素抵抗的发展提供重要的见解。这篇综述将讨论关于脂联素寡聚体的生化组成、常用的分析技术以及影响其组装的已知翻译后修饰的最新知识。将考虑基于体外寡聚体组装反应的证据，以支持脂联素寡聚体形成的“胱氨酸棘轮”模型，以及该证据的局限性。还将讨论已显示影响脂联素寡聚体分布的分泌途径蛋白，并提出它们可能参与脂联素寡聚化的胱氨酸棘轮模型的假说。
