| Written | 2009-05 | Virginia Kaklamani, Christos Mantzoros |
| | Department of Medicine, Division of Hematology/Oncology, Northwestern University, Feinberg School of Medicine, Chicago, IL, 676 N St Clair St. Suite 850, Chicago, IL 60611, USA (VK); Department of Medicine, Division of Endocrinology, Harvard University Medical School, Beth Israel Deaconess Medical Center, E/St 816, 330 Brookline Ave, Boston, MA02215, USA (CM) |
| Description | Receptor for globular and full-length adiponectin (APM1), an essential hormone secreted by adipocytes that counteracts the effects of insulin. |
| Expression | Widely expressed. Highly expressed in adipose tissue and skeletal muscle. Expressed at intermediate level in brain, heart, spleen, kidney, liver, placenta, lung and peripheral blood leukocytes. Weakly expressed in colon, thymus and small intestine. We have also shown expression in normal and cancerous breast tissue as well as in other cancers such as prostate, colon, endometrial. It is also present in several cell lines. |
| Localisation | ADIPOR1 localizes to the plasma membrane. |
| Function | Receptor for globular and full-length adiponectin (APM1), an essential hormone secreted by adipocytes that acts as an antidiabetic. Probably involved in metabolic pathways that regulate lipid metabolism such as fatty acid oxidation. Mediates increased AMPK, PPARa ligand activity, fatty acid oxidation and glucose uptake by adiponectin. Has some high-affinity for globular adiponectin but low-affinity for full-length adiponectin. |
| Homology | The mouse, human, and rat Adipor1 protein (ADIPOR1) contains 375 amino acids. Human and mouse ADIPOR1 share 96.8% identity. |
| Note | |
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| Entity | Breast Cancer |
| Note | Adiponectin has been implicated in breast cancer. The breast cancer cell lines MCF-7, MDB-MB-231 and T47D were found to express both adiponectin receptors ADIPOR1/ADIPOR2 (Dieudonne et al., 2006; Korner et al., 2007) and exposure of T47D cells to adiponectin, significantly inhibited their proliferation (Korner et al., 2007). rs2232853 CT genotype (OR=1.67; 95% CI 1.23-2.26) and the combination of rs7539542 GC (OR=0.59; 95% CI 0.36-0.98) and CC genotypes (OR=0.57; 95% CI 0.35-0.94) were significantly associated with breast cancer risk. The high expressing rs2241766 G allele (GG and GT genotypes) was associated with decreased breast cancer risk (OR=0.64; 95% CI 0.49-0.83). The low expressing rs1501299 G allele was associated with increased breast cancer risk: for TG: OR=1.59; 95% CI 1.03-2.48, for GG: OR= 1.80; 95% CI 1.14-2.85. |
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| Entity | Colon Cancer |
| Note | Adiponectin has also been implicated in colon cancer risk. rs266729 polymorphism was significantly associated with colon cancer risk: the RR for the GG/CG genotypes was rs266729 was associated with a reduced colorectal cancer risk: O.R. 0.73, 95% CI (0.53-0.99) (Kaklamani et al., 2008). |
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| Entity | Endometrial Cancer |
| Note | Adiponectin levels have been shown to correlate with endometrial cancer risk (Petridou et al., 2003; Dal et al., 2004). |
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| Entity | Prostate Cancer |
| Note | Adiponectin levels have been shown to correlate with prostate cancer risk (Barb et al., 2007; Arisan et al., 2009). |
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| Serum adipocytokine levels in prostate cancer patients. |
| Arisan ED, Arisan S, Atis G, Palavan-Unsal N, Ergenekon E. |
| Urol Int. 2009;82(2):203-8. Epub 2009 Mar 19. |
| PMID 19322011 |
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| Adiponectin in relation to malignancies: a review of existing basic research and clinical evidence. |
| Barb D, Williams CJ, Neuwirth AK, Mantzoros CS. |
| Am J Clin Nutr. 2007 Sep;86(3):s858-66. |
| PMID 18265479 |
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| Circulating adiponectin and endometrial cancer risk. |
| Dal Maso L, Augustin LS, Karalis A, Talamini R, Franceschi S, Trichopoulos D, Mantzoros CS, La Vecchia C. |
| J Clin Endocrinol Metab. 2004 Mar;89(3):1160-3. |
| PMID 15001602 |
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| Adiponectin mediates antiproliferative and apoptotic responses in human MCF7 breast cancer cells. |
| Dieudonne MN, Bussiere M, Dos Santos E, Leneveu MC, Giudicelli Y, Pecquery R. |
| Biochem Biophys Res Commun. 2006 Jun 23;345(1):271-9. Epub 2006 Apr 27. |
| PMID 16678125 |
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| Variants of the adiponectin (ADIPOQ) and adiponectin receptor 1 (ADIPOR1) genes and colorectal cancer risk. |
| Kaklamani VG, Wisinski KB, Sadim M, Gulden C, Do A, Offit K, Baron JA, Ahsan H, Mantzoros C, Pasche B. |
| JAMA. 2008 Oct 1;300(13):1523-31. |
| PMID 18827209 |
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| Total and high-molecular-weight adiponectin in breast cancer: in vitro and in vivo studies. |
| Korner A, Pazaitou-Panayiotou K, Kelesidis T, Kelesidis I, Williams CJ, Kaprara A, Bullen J, Neuwirth A, Tseleni S, Mitsiades N, Kiess W, Mantzoros CS. |
| J Clin Endocrinol Metab. 2007 Mar;92(3):1041-8. Epub 2006 Dec 27. |
| PMID 17192291 |
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| Plasma adiponectin concentrations in relation to endometrial cancer: a case-control study in Greece. |
| Petridou E, Mantzoros C, Dessypris N, Koukoulomatis P, Addy C, Voulgaris Z, Chrousos G, Trichopoulos D. |
| J Clin Endocrinol Metab. 2003 Mar;88(3):993-7. |
| PMID 12629074 |
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| Common haplotypes at the adiponectin receptor 1 (ADIPOR1) locus are associated with increased risk of coronary artery disease in type 2 diabetes. |
| Soccio T, Zhang YY, Bacci S, Mlynarski W, Placha G, Raggio G, Di Paola R, Marucci A, Johnstone MT, Gervino EV, Abumrad NA, Klein S, Trischitta V, Doria A. |
| Diabetes. 2006 Oct;55(10):2763-70. |
| PMID 17003341 |
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