Important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities. Stimulates AMPK phosphorylation and activation in the liver and the skeletal muscle, enhancing glucose utilization and fatty-acid combustion. Antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. Inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. May play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW (By similarity). Polymerization and secretion of adiponectin is inhibited by succination of cysteine residues by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues. Homomultimer. Forms trimers, hexamers and 12- to 18-mers. The trimers (low molecular weight complexes / LMW) are assembled via non-covalent interactions of the collagen-like domains in a triple helix and hydrophobic interactions within the globular C1q domain. Several trimers can associate to form disulfide-linked hexamers (middle molecular weight complexes / MMW) and larger complexes (higher molecular weight / HMW). The HMW-complex assembly is also modulated by the degree of lysine hydroxylation and glycosylation. LMW, MMW and HMW complexes bind to HBEGF, MMW and HMW complexes bind to PDGFB, and HMW complex binds to FGF2. Interacts with CTRP9 via the C1q domain (heterotrimeric complex). HMW complexes are more extensively glycosylated than smaller oligomers. Hydroxylation and glycosylation of the lysine residues within the collagen-like domain of adiponectin seem to be critically involved in regulating the formation and/or secretion of HMW complexes and consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes. O-glycosylated. O-linked glycans on hydroxylysine residues consist of Glc-Gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups (By similarity). O-linked glycosylations elsewhere disialylated with the structure Neu5Acalpha2->8Neu5Acalpha2->3Gal. Sialylated by alpha 2,8-sialyltransferase III. Desialylated forms are rapidly cleared from the circulation. Not N-glycosylated. Succination of Cys-31 by the Krebs cycle intermediate fumarate, which leads to S-(2-succinyl)cysteine residues, inhibits polymerization and secretion of adiponectin. Adiponectin is a major target for succination in both adipocytes and adipose tissue of diabetic mammals. It was proposed that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes. HMW-complex blood contents are higher in females than in males, are increased in males by castration and decreased again upon subsequent testosterone treatment, which blocks HMW-complex secretion.