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)
Jump to navigation
Jump to search
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
Expression
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]
Polymorphism
- genetic variations in ADIPOQ influence the variance in adiponectin serum levels & define the adiponectin serum levels quantitative trait locus 1 (ADIPQTL1) [MIM:612556]
Pharmacology
- adiponectin might be useful in the treatment of diabetes mellitus type 2 & insulin resistance
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]
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
More general terms
References
- ↑ Barbara Hansen, University of Maryland, AGE Meeting, Madison, WI, June 2001
- ↑ 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: https://www.ncbi.nlm.nih.gov/pubmed/11479628
- ↑ UniProt http://www.uniprot.org/uniprot/Q15848.html
- ↑ Wikipedia; Note: adiponectin entry http://en.wikipedia.org/wiki/adiponectin
- ↑ 5.0 5.1 5.2 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: https://www.ncbi.nlm.nih.gov/pubmed/24172895
- ↑ 6.0 6.1 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 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26903641 <Internet> http://www.pnas.org/content/113/10/2708
Database
- Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9370
- Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9370
- OMIM: https://mirror.omim.org/entry/125853
- OMIM: https://mirror.omim.org/entry/605441
- OMIM: https://mirror.omim.org/entry/612556
- UniProt: http://www.uniprot.org/uniprot/Q15848.html