adiponectin

Adiponectin is a circulating adipokine produced predominantly by adipose tissue. It is one of the most abundant proteins in plasma and plays a central role in regulating glucose levels and fatty acid oxidation. The gene ADIPOQ on chromosome 3 encodes adiponectin, and circulating levels are influenced by body fat, nutritional status, and metabolic disease.

Adiponectin is secreted as a full-length protein that forms multimers, including trimers, hexamers, and high-molecular-weight complexes. The protein undergoes post-translational modifications such as hydroxylation and glycosylation, which affect multimerization and receptor interaction. Serum adiponectin concentrations are typically measured in micrograms per milliliter and are usually lower in obesity than in lean individuals.

Adiponectin signals through its receptors AdipoR1 and AdipoR2, with T-cadherin contributing to binding of some multimeric forms. The receptors possess intrinsic ceramidase activity, which can shift lipid signaling toward sphingosine-1-phosphate. Receptor activation engages pathways including AMPK and PPAR-alpha, increasing fatty acid oxidation and reducing hepatic glucose production.

Physiologically, adiponectin improves insulin sensitivity, promotes glucose uptake in skeletal muscle, and suppresses hepatic gluconeogenesis. It also exerts anti-inflammatory effects on macrophages and can influence energy expenditure and lipid metabolism, contributing to protection against metabolic syndrome and atherosclerosis in some contexts.

Clinical significance: lower adiponectin levels are associated with obesity, type 2 diabetes, and increased cardiovascular risk, while higher levels correlate with better metabolic health. Therapies that raise adiponectin, such as thiazolidinediones, or experimental adiponectin receptor agonists are explored as treatments for insulin resistance. Adiponectin is also studied as a biomarker for metabolic disease severity and treatment response.