Adiponectin self-regulates its expression and multimerization in adipose tissue: an autocrine/paracrine mechanism?

Adiponectin, a 30-kDa peptide hormone discovered in the mid 1990s, is secreted abundantly and exclusively by adipose tissue. Adiponectin exists in three major forms: a low molecular weight (LMW) trimer, a medium molecular weight (MMW) hexamer, and a high molecular weight (HMW) 18-36 oligomer. The HMW oligomer has the most potent insulin-sensitizing activity therefore impaired adiponectin multimerization may lead to impaired glycemic control. Decreased ratio of HMW/total adiponectin has been observed in patients with obesity, type-2 diabetes mellitus, cardiovascular diseases and insulin resistance-related metabolic syndrome. Previous studies have indicated that berberine or aminoimidazole carboxamide ribonucleotide (AICAR)-induced activation of AMP-activated protein kinase (AMPK) suppresses the expression of adiponectin but promotes adiponectin multimerization in adipocytes. Since adiponectin activates AMPK through adiponectin receptors (AdipoRs) in the membranes of adipocytes, we speculate that adiponectin self-regulates its expression and multimerization in adipose tissue. The hypothesis suggests a potential drug target for treating insulin resistance and provides new interpretation of several clinical observations. In addition, we propose a rapid method for one-step detection of the distribution of adiponectin oligomers in approximately 30 min, based on the open sandwich immunoassay and fluorescence resonance energy transfer technology. With the development of this new method, the ratio of HMW/total adiponectin may be applied in clinical diagnosis as a novel biomarker for insulin resistance and metabolic disorders.