Adiponectin is an insulin-sensitizing adipokine with anti-diabetic, anti-atherogenic, anti-inflammatory and cardioprotective properties. This adipokine is secreted from adipocytes into the circulation as three oligomeric isoforms, including trimeric, hexameric and the HMW (high-molecular-mass) oligomeric complex consisting of at least 18 protomers. Each oligomeric isoform of adiponectin exerts distinct biological properties in its various target tissues. The HMW oligomer is the major active form mediating the insulin-sensitizing effects of adiponectin, whereas the central actions of this adipokine are attributed primarily to the hexameric and trimeric oligomers. In patients with Type 2 diabetes and coronary heart disease, circulating levels of HMW adiponectin are selectively decreased due to an impaired secretion of this oligomer from adipocytes. The biosynthesis of the adiponectin oligomers is a complex process involving extensive post-translational modifications. Hydroxylation and glycosylation of several conserved lysine residues in the collagenous domain of adiponectin are necessary for the intracellular assembly and stabilization of its high-order oligomeric structures. Secretion of the adiponectin oligomers is tightly controlled by a pair of molecular chaperones in the ER (endoplasmic reticulum), including ERp44 (ER protein of 44 kDa) and Ero1-Lα (ER oxidoreductase 1-Lα). ERp44 inhibits the secretion of adiponectin oligomers through a thiol-mediated retention. In contrast, Ero1-Lα releases HMW adiponectin trapped by ERp44. The PPARγ (peroxisome-proliferator-activated receptor γ) agonists thiazolidinediones selectively enhance the secretion of HMW adiponectin through up-regulation of Ero1-Lα. In the present review, we discuss the recent advances in our understanding of the structural and biological properties of the adiponectin oligomeric isoforms and highlight the role of post-translational modifications in regulating the biosynthesis of HMW adiponectin.
Review Article| January 15 2008
Post-translational modifications of adiponectin: mechanisms and functional implications
Karen S. L. Lam;
Aimin Xu 1
†Research Center for Heart, Brain, Hormone and Healthy Ageing, University of Hong Kong, Hong Kong, China
‡Department of Medicine, University of Hong Kong, Hong Kong, China
§Department of Pharmacology, University of Hong Kong, Hong Kong, China
1To whom correspondence should be addressed (email email@example.com).
Search for other works by this author on:
- Views Icon Views
- Share Icon Share
- Cite Icon Cite
Yu Wang, Karen S. L. Lam, Ming-hon Yau, Aimin Xu; Post-translational modifications of adiponectin: mechanisms and functional implications. Biochem J 1 February 2008; 409 (3): 623–633. doi: https://doi.org/10.1042/BJ20071492
Download citation file: