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Published on: May 4, 2021
Post-translational modifications of adiponectin: mechanisms and functional implications
Yu Wang1, Karen S L Lam, Ming-hon Yau
1Genome Research Center, University of Hong Kong, Hong Kong, China.
The Biochemical Journal
|January 8, 2008
Summary
Adiponectin, an insulin-sensitizing adipokine, exists in various forms. High-molecular-mass adiponectin is crucial for insulin sensitivity but is reduced in diabetes and heart disease.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Adiponectin is an insulin-sensitizing adipokine with anti-diabetic, anti-atherogenic, anti-inflammatory, and cardioprotective effects.
- It circulates as trimeric, hexameric, and high-molecular-mass (HMW) oligomeric isoforms, each with distinct biological activities.
- HMW adiponectin is the primary form mediating insulin-sensitizing effects, while hexameric and trimeric forms are central to other actions.
Purpose of the Study:
- To review recent advances in understanding the structural and biological properties of adiponectin oligomeric isoforms.
- To highlight the role of post-translational modifications in regulating the biosynthesis of HMW adiponectin.
- To discuss the mechanisms controlling adiponectin oligomer secretion.
Main Methods:
- The review synthesizes current research on adiponectin structure, function, and biosynthesis.
- It examines the impact of post-translational modifications like hydroxylation and glycosylation on oligomer assembly.
- The role of endoplasmic reticulum chaperones ERp44 and Ero1-Lalpha in regulating adiponectin secretion is discussed.
Main Results:
- Hydroxylation and glycosylation are essential for the intracellular assembly and stabilization of HMW adiponectin.
- ERp44 inhibits adiponectin secretion via thiol-mediated retention, while Ero1-Lalpha facilitates HMW adiponectin release.
- PPARgamma agonists like thiazolidinediones enhance HMW adiponectin secretion by up-regulating Ero1-Lalpha.
Conclusions:
- Adiponectin oligomer biosynthesis is a complex, tightly regulated process involving post-translational modifications and specific molecular chaperones.
- Understanding these mechanisms is crucial, as impaired HMW adiponectin secretion is linked to Type 2 diabetes and coronary heart disease.
- Targeting the Ero1-Lalpha pathway may offer therapeutic strategies to improve HMW adiponectin levels and associated metabolic conditions.
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