Assembly of adiponectin oligomers.

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.