Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein which in humans is encoded by the ADIPOQgene. It is involved in regulating glucose levels as well as fatty acid breakdown.
Adiponectin is a 244-amino-acid-long polypeptide. There are four distinct regions of adiponectin. The first is a short signal sequence that targets the hormone for secretion outside the cell; next is a short region that varies between species; the third is a 65-amino acid region with similarity to collagenous proteins; the last is a globular domain. Overall this gene shows similarity to the complement 1Q factors (C1Q). However, when the 3-dimensional structure of the globular region was determined, a striking similarity to TNFα was observed, despite unrelated protein sequences.
Adiponectin is secreted into the bloodstream where it accounts for approximately 0.01% of all plasma protein at around 5-10 μg/mL. Plasma concentrations reveal a sexual dimorphism, with females having higher levels than males. Levels of adiponectin are reduced in diabetics compared to non-diabetics. Weight reduction significantly increases circulating levels.
Adiponectin automatically self-associates into larger structures. Initially, three adiponectin molecules bind together to form a homotrimer. The trimers continue to self-associate and form hexamers or dodecamers. Like the plasma concentration, the relative levels of the higher-order structures are sexually dimorphic, where females have increased proportions of the high-molecular weight forms. Recent studies showed that the high-molecular weight form may be the most biologically active form regarding glucose homeostasis. High-molecular-weight adiponectin was further found to be associated with a lower risk of diabetes with similar magnitude of association as total adiponectin. However, coronary artery disease has been found to be positively associated with high molecular weight adiponectin, but not with low molecular weight adiponectin.
Adiponectin exerts some of its weight reduction effects via the brain. This is similar to the action of leptin, but the two hormones perform complementary actions, and can have synergistic effects.
These have distinct tissue specificities within the body and have different affinities to the various forms of adiponectin. The receptors affect the downstream target AMP kinase, an important cellular metabolic rate control point. Expression of the receptors is correlated with insulin levels, as well as reduced in mouse models of diabetes, particularly in skeletal muscle and adipose tissue.
Adiponectin was first characterised in 1995 in differentiating 3T3-L1 adipocytes (Scherer PE et al). In 1996 it was characterised in mice as the mRNA transcript most highly expressed in adipocytes(Maeda, 1996 ((citation #1, below))). In 2007, adiponectin was identified as an transcript highly expressed in preadipocytes (precursors of fat cells) differentiating into adipocytes.
The human homologue was identified as the most abundant transcript in adipose tissue. Contrary to expectations, despite being produced in adipose tissue, adiponectin was found to be decreased in obesity. This downregulation has not been fully explained. The gene was localised to chromosome 3q27, a region highlighted as affecting genetic susceptibility to type 2 diabetes and obesity. Supplementation by differing forms of adiponectin were able to improve insulin control, blood glucose and triglyceride levels in mouse models.
Because this substance is a protein, oral administration of adiponectin is not effective, as enzymes in the digestive system break it down into its constituent amino-acid parts. One way to introduce the hormone into the blood stream is intravenous administration, which itself poses significant logistical challenges.
Sweet potatoes are known to contain adiponectin. A scientific study has supported the idea that extracts of sweet potatoes can raise levels of adiponectin in humans. Although there is doubt in the scientific community about the reliability of this evidence.
This section requires expansion. (May 2013)
^Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (April 1996). "cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1)". Biochem. Biophys. Res. Commun.221 (2): 286–9. doi:10.1006/bbrc.1996.0587. PMID8619847.
^Shapiro L, Scherer PE (March 1998). "The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor". Curr. Biol.8 (6): 335–8. doi:10.1016/S0960-9822(98)70133-2. PMID9512423.
^Chen J, et al. (June 2006). "Secretion of adiponectin by human placenta: differential modulation of adiponectin and its receptors by cytokines.". Diabetalogica49 (6): 1292–302. doi:10.1007/s00125-006-0194-7. PMID16570162.
^ abBauche IB, El Mkadem SA, Pottier AM, Senou M, Many MC, Rezsohazy R, Penicaud L, Maeda N, Funahashi T, Brichard SM (April 2007). "Overexpression of adiponectin targeted to adipose tissue in transgenic mice: impaired adipocyte differentiation". Endocrinology148 (4): 1539–49. doi:10.1210/en.2006-0838. PMID17204560.
^ abRenaldi O, Pramono B, Sinorita H, Purnomo LB, Asdie RH, Asdie AH (January 2009). "Hypoadiponectinemia: a risk factor for metabolic syndrome". Acta Med Indones41 (1): 20–4. PMID19258676.
^Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (August 2001). "The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity". Nat. Med.7 (8): 941–6. doi:10.1038/90984. PMID11479627.
^Coppola A, Marfella R, Coppola L, Tagliamonte E, Fontana D, Liguori E, Cirillo T, Cafiero M, Natale S, Astarita C (March 2008). "Effect of weight loss on coronary circulation and adiponectin levels in obese women". Int. J. Cardiol.134 (3): 414–6. doi:10.1016/j.ijcard.2007.12.087. PMID18378021.
^Oh DK, Ciaraldi T, Henry RR Adiponectin in health and disease. Diabetes Obes Metab 2007:9:282–289
^Rizza S, Gigli F, Galli A, Micchelini B, Lauro D, Lauro R, Federici M (2010). "Adiponectin isoforms in elderly patients with or without coronary artery disease". JOURNAL OF THE AMERICAN GERIATRIC SOCIETY58 (4): 702–706. doi:10.1111/j.1532-5415.2010.02773.x. PMID20398150.
^Fang X, Sweeney G (November 2006). "Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes". Biochem. Soc. Trans.34 (Pt 5): 798–801. doi:10.1042/BST0340798. PMID17052201.
^Bonnard C, Durand A, Vidal H, Rieusset J (February 2008). "Changes in adiponectin, its receptors and AMPK activity in tissues of diet-induced diabetic mice". Diabetes Metab.34 (1): 52–61. doi:10.1016/j.diabet.2007.09.006. PMID18222103.
^Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem. 1995 Nov 10;270(45):26746-9. PMID 7592907
^ abcdLara-Castro C, Fu Y, Chung BH, Garvey WT (June 2007). "Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease". Curr. Opin. Lipidol.18 (3): 263–70. doi:10.1097/MOL.0b013e32814a645f. PMID17495599.
^ abVasseur F, Meyre D, Froguel P (2006). "Adiponectin, type 2 diabetes and the metabolic syndrome: lessons from human genetic studies". Expert Rev Mol Med8 (27): 1–12. doi:10.1017/S1462399406000147. PMID17112391.
^Grimshaw CE, Matthews DA, Varughese KI, Skinner M, Xuong NH, Bray T, Hoch J, Whiteley JM (August 1992). "Characterization and nucleotide binding properties of a mutant dihydropteridine reductase containing an aspartate 37-isoleucine replacement". J. Biol. Chem.267 (22): 15334–9. PMID1639779.
^Yuan J, Liu W, Liu ZL, Li N (2006). "cDNA cloning, genomic structure, chromosomal mapping and expression analysis of ADIPOQ (adiponectin) in chicken". Cytogenet Genome Res112 (1-2): 148–51. doi:10.1159/000087527. PMID16276104.
^Nishio S, Gibert Y, Bernard L, Brunet F, Triqueneaux G, Laudet V (2008). "Adiponectin and adiponectin receptor genes are coexpressed during zebrafish embryogenesis and regulated by food deprivation". Dev Dyn237 (6): 1682–90. doi:10.1002/dvdy.21559. PMID18489000.