ADIPOQ

ADIPOQ is the gene that encodes adiponectin, a hormone-like protein produced predominantly by adipose tissue. Located on chromosome 3q27, the ADIPOQ gene provides instructions for making adiponectin, which is secreted into the bloodstream in various multimeric forms. Adiponectin is mainly expressed in white adipose tissue but is also found at lower levels in other tissues.

The adiponectin protein contains a signal peptide, a collagen-like domain, and a globular domain. After synthesis, it assembles into distinct multimeric complexes: low molecular weight trimers, medium molecular weight hexamers, and high molecular weight multimers. Post-translational modifications, including hydroxylation and glycosylation of lysine residues in the collagenous domain, are important for proper multimerization and function. The different forms have varying biological activities and receptor affinities.

Adiponectin acts through two main receptors, AdipoR1 and AdipoR2, which are widely expressed in metabolic tissues. Signaling via these receptors activates pathways such as AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor alpha (PPAR-α), promoting fatty acid oxidation and improved insulin sensitivity. AdipoR1 is enriched in skeletal muscle, while AdipoR2 is more prominent in the liver. The receptors may also have ceramidase activity, reducing ceramide levels and contributing to anti-apoptotic and anti-inflammatory effects.

Clinical relevance of ADIPOQ includes its association with metabolic health. Circulating adiponectin levels are typically reduced in obesity, insulin resistance, and type 2 diabetes, and they rise with weight loss. Pharmacological agents such as thiazolidinediones can increase adiponectin levels. Genetic variants in ADIPOQ influence circulating adiponectin and may modulate risk for obesity-related diseases across populations.