What is Adiponectin
Adiponectin is an adipose-specific hormone with anti-inflammatory and insulin-sensitizing properties that, uniquely among adipokines, is protective against obesity and its metabolic complications. 1
Basic Structure and Secretion
- Adiponectin is a protein consisting of 244 amino acids with a molecular weight of 28 kDa, secreted predominantly by adipose tissue (both white and brown). 2
- It circulates in the blood in three different molecular weight forms: low, medium, and high-molecular-weight complexes, with the high-molecular-weight form appearing to be the most metabolically active and pathogenic. 1
- Its secretion from adipocytes is regulated by peroxisomal proliferator-activated receptor (PPAR)-γ. 1
Unique Inverse Relationship with Obesity
- In stark contrast to other adipokines, adiponectin levels are inversely proportional to body fat content—meaning leaner individuals have higher levels while obese individuals have lower levels. 3
- Higher adiponectin correlates with leanness, lower C-reactive protein (CRP), lower carotid intima-media thickness, and improved insulin sensitivity. 1
- Longitudinal decreases in adiponectin are seen with increasing adiposity, and adiponectin levels predict type 2 diabetes mellitus (T2DM) in obese children. 1
Metabolic and Anti-Inflammatory Functions
- Adiponectin plays a central role in glucose and lipid metabolism by increasing insulin sensitivity and improving systemic lipid metabolism. 4
- It has direct actions in liver, skeletal muscle, and the vasculature, with prominent roles to improve hepatic insulin sensitivity, increase fuel oxidation via up-regulation of AMPK activity, and decrease vascular inflammation. 3
- The hormone exhibits anti-inflammatory, anti-fibrotic, and antioxidant effects throughout the body. 4
Receptor System
- Adiponectin effects are mediated via two receptors: AdipoR1 (most highly expressed in skeletal muscle) and AdipoR2 (most highly expressed in liver). 3
- AdipoR1 has a prominent action to activate AMPK and promote lipid oxidation in muscle. 3
- AdipoR2 enhances insulin sensitivity and reduces hepatic steatosis via activation of AMPK and increased PPAR-α ligand activity. 3
Clinical Associations
- In adults, adiponectin has independent negative associations with obesity, hyperinsulinemia and insulin resistance, metabolic syndrome, visceral adiposity, T2DM, and coronary artery disease. 1
- In children, plasma adiponectin concentrations show inverse correlation with adiposity, insulin resistance, hepatic fat by MRI, and carotid intima-media thickness. 1
- Some studies demonstrate an inverse relationship between adiponectin and CRP, even after adjustment for pubertal status, insulin resistance, and BMI, suggesting a regulatory interaction independent of insulin sensitivity. 1
Therapeutic Implications
- Thiazolidinediones (used to treat T2DM) act in part by increasing levels of adiponectin. 1
- Adult weight loss through dieting or bariatric surgery is associated with increased adiponectin levels. 1
- Adiponectin is favorably modifiable by simple lifestyle changes—intervention studies have shown increases in adiponectin levels with or without weight reduction and with increasing physical fitness, mostly related to improvements in insulin resistance and inflammatory factors. 1
- Adiponectin represents a potential therapeutic target in the treatment of diabetes mellitus and other diseases associated with hypoadiponectinemia. 5
Important Clinical Caveat
- High-molecular-weight adiponectin (rather than total adiponectin) better reflects metabolic abnormalities associated with childhood obesity, making it a more precise biomarker when available. 1