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adiponectin; 30 kD adipocyte complement-related protein; adipocyte complement-related 30 kD protein; ACRP30; adipocyte, C1q & collagen domain-containing protein; adipose most abundant gene transcript 1 protein; apM-1; Gelatin-binding protein (ADIPOQ, ACDC, ACRP30, APM1, GBP28)

Function: - adipokine involved in the control of fat metabolism & insulin sensitivity, with direct anti-diabetic, anti-atherogenic & anti-inflammatory activities - enhances insulin sensitivity of muscle & liver cells - the combination of adiponectin & leptin is more potent than either protein alone - stimulates AMPK phosphorylation & activation in the liver & skeletal muscle, enhancing glucose utilization & fatty-acid oxidation - antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver & macrophages, & also by counteracting its effects. inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway - may play a role in cell growth, angiogenesis & tissue remodeling by binding & sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW Structure: - O-glycosylated - not N-glycosylated - O-linked glycans on hydroxylysines consist of Glc-gal disaccharides bound to the oxygen atom of post-translationally added hydroxyl groups - sialylated to varying degrees depending on tissue - Thr-22 appears to be the major site of sialylation - higher sialylation found in SGBS adipocytes than in HEK fibroblast - sialylation is not required for heterodimerization or for secretion - not sialylated on the glycosylated hydroxylysines - desialylated forms are rapidly cleared from the circulation - homomultimer - forms trimers, hexamers & 12- to 18-mers - the trimers (LMW complexes are assembled via non-covalent interactions of the collagen-like domains in a triple helix & hydrophobic interactions within the globular C1q domain - several trimers can associate to form disulfide-linked hexamers (MMW complexes) & larger complexes (HMW complex) - the HMW complex assembly may rely aditionally on Lys hydroxylation & glycosylation - LMW, MMW & HMW complexes bind to HBEGF, MMW & HMW complexes bind to PDGFB, & HMW complex binds to FGF2 - HMW complexes are more extensively glycosylated than smaller oligomers - hydroxylation & glycosylation of the Lys within the collagen-like domain of adiponectin seem to be involved in regulating formation &/or secretion of HMW complexes & consequently contribute to the insulin-sensitizing activity of adiponectin in hepatocytes - interacts with CTRP9A via the C1q domain (heterotrimeric complex) - the C1q domain is commonly called the globular domain - contains 1 C1q domain - contains 1 collagen-like domain Compartment: secreted, plasma Expression: - secreted into plasma from apipocytes Polymorphism: - genetic variations in ADIPOQ influence the variance in adiponectin serum levels & define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556] Pathology: - defects in ADIPOQ are the cause of adiponectin deficiency - genetic variations in ADIPOQ are associated with diabetes mellitus type 2 - low levels of adiponectin are associated with obesity, insulin resistance, & diabetes mellitus type 2 [5] Pharmacology: - adiponectin might be useful in the treatment of diabetes mellitus type 2 & insulin resistance Notes: - variants Arg-84 & Ser-90 show impaired formation of HMW complexes whereas variants Cys-112 & Thr-164 show impaired secretion of adiponectin in any form - HMW-complex blood contents are higher in females than in males, are increased in males by castration & decreased again upon subsequent testosterone treatment, which blocks HMW-complex secretion (putative) - in patients with diabetes mellitus type 2 both the ratios of HMW to total adiponectin & the degree of adiponectin glycosylation are significantly decreased as compared with healthy controls Comparative biology: - decreased plasma levels observed in insulin-resistant mice - treatment of insulin-resistant mice with physiologic levels of adiponectin results in enhanced insulin sensitivity, by increasing fatty acid catabolism & energy dissipation - raising circulating levels of adiponectin with a small molecule AdipoRon protects mice against insulin resistance & glucose intolerance [5] - administration of adiponectin rescues DHEA-induced polycystic ovarian disease phenotype in a rat model [6]

General

adipokine

Properties

SIZE: entity length = 244 aa MW = 26 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-18} Thr glycosylation site {T21} Thr glycosylation site {T22} cysteine residue {C36} MODIFICATION: cysteine residue {CINTERCHAIN; IN FORM MMW AND FORM HMW} Collagen-like {42-107} MOTIF: proline residue {62} proline residue {86} proline residue {104} C1q {108-244} MOTIF: asparagine residue {230}

Database Correlations

OMIM correlations UniProt Q15848 PFAM correlations Entrez Gene 9370 Kegg hsa:9370

References

  1. Barbara Hansen, University of Maryland, AGE Meeting, Madison, WI, June 2001
  2. Journal Watch 21(17):141, 2001 Berg AH et al The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947, 2001 PMID: 11479628
  3. UniProt :accession Q15848
  4. Wikipedia; Note: adiponectin entry http://en.wikipedia.org/wiki/adiponectin
  5. Okada-Iwabu M et al. A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 2013 Nov 28; 503:493 PMID: 24172895
  6. Komaroff AL Understanding the Pathogenesis of Polycystic Ovary Syndrome NEJM Journal Watch. March 10, 2015 Massachusetts Medical Society (subscription needed) http://www.jwatch.org - Yuan X et al. Brown adipose tissue transplantation ameliorates polycystic ovary syndrome. Proc Natl Acad Sci U S A 2016 Mar 8; 113:2708 PMID: 26903641 http://www.pnas.org/content/113/10/2708