Journal of Molecular Medicine

, Volume 81, Issue 7, pp 428–434

Allele-specific differential expression of a common adiponectin gene polymorphism related to obesity

  • Wei-Shiung Yang
  • Pei-Ling Tsou
  • Wei-Jei Lee
  • Da-Lun Tseng
  • Chi-Ling Chen
  • Chi-Chung Peng
  • Kuan-Ching Lee
  • Mei-Ju Chen
  • Chang-Jen Huang
  • Tong-Yuan Tai
  • Lee-Ming Chuang
Original Article


Adiponectin gene polymorphisms have recently been reported to be associated with obesity, insulin sensitivity, and the risk of type 2 diabetes. We examined a T94G polymorphism of the adiponectin gene in 245 ostensibly normal nondiabetic subjects. The G allele frequency was lower among subjects with higher BMI (≥27) than in those with lower BMI. BMI was inversely correlated with the dose of G allele. Multivariate linear regression analyses showed that the adiponectin genotypes were significantly related to BMI after adjusting for age and gender. The dose of the G allele was associated with a reduction of approximately 1.12 kg/m2 in BMI. We further found that the relative mRNA levels of G allele were consistently higher than those of T allele in the omental adipose tissue from 21 heterozygous subjects. Finally, we observed that the expression levels of adiponectin affected insulin-stimulated glucose uptake in differentiated 3T3-L1 adipocytes. In conclusion, the allele-specific differential expression of this common polymorphism could be responsible for its biological effects observed in this and the other studies.


Obesity Insulin resistance Adiponectin Polymorphism mRNA 



Body mass index


Single nucleotide polymorphism


  1. 1.
    Funahashi T, Nakamura T, Shimomura I, Maeda K, Kuriyama H, Takahashi M, Arita Y, Kihara S, Matsuzawa Y (1999) Role of adipocytokines on the pathogenesis of atherosclerosis in visceral obesity. Intern Med 3:202–206Google Scholar
  2. 2.
    Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395:763–770PubMedGoogle Scholar
  3. 3.
    Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Laza, MA (2001) The hormone resistin links diabetes to obesity. Nature 409:307–312CrossRefPubMedGoogle Scholar
  4. 4.
    Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipocyte-specific gene dysregulated in obesity. J Biol Chem 271:10697–10703PubMedGoogle Scholar
  5. 5.
    Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270:26746–26749PubMedGoogle Scholar
  6. 6.
    Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K (1996) cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1. Biochem Biophys Res Commun 221:286–289PubMedGoogle Scholar
  7. 7.
    Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M (1996) Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem (Tokyo) 120:803–812Google Scholar
  8. 8.
    Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (1999) Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100:2473–2476PubMedGoogle Scholar
  9. 9.
    Yokota T, Oritani K, Takahashi I, Ishikawa J, Matsuyama A, Ouchi N, Kihara S, Funahashi T, Tenner AJ, Tomiyama Y, Matsuzawa Y (2000) Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood 96:1723–1732PubMedGoogle Scholar
  10. 10.
    Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 12:1296–1301Google Scholar
  11. 11.
    Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, Ishigami M, Kuriyama H, Kishida K, Nishizawa H, Hotta K, Muraguchi M, Ohmoto Y, Yamashita S, Funahashi T, Matsuzawa Y (2001) Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 103:1057–1063PubMedGoogle Scholar
  12. 12.
    Okamoto Y, Arita Y, Nishida M, Muraguchi M, Ouchi N, Takahashi M, Igura T, Inui Y, Kihara S, Nakamura T, Yamashita S, Miyagawa J, Funahashi T, Matsuzawa Y (2000) An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 32:47–50PubMedGoogle Scholar
  13. 13.
    Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, Matsuzawa Y (2001) Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 50:1126–1133PubMedGoogle Scholar
  14. 14.
    Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, Bihain BE, Lodish HF (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 98:2005–2010CrossRefPubMedGoogle Scholar
  15. 15.
    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 (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–746PubMedGoogle Scholar
  16. 16.
    Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7:947–953PubMedGoogle Scholar
  17. 17.
    Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257:79–83PubMedGoogle Scholar
  18. 18.
    Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595–1599Google Scholar
  19. 19.
    Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, Tataranni PA (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930–1935PubMedGoogle Scholar
  20. 20.
    Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, Yamauchi T, Otabe S, Okada T, Eto K, Kadowaki H, Hagura R, Akanuma Y, Yazaki Y, Nagai R, Taniyama M, Matsubara K, Yoda M, Nakano Y, Kimura S, Tomita M, Kimura S, Ito C, Froguel P, Kadowaki T (2002) Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes 51:536–540PubMedGoogle Scholar
  21. 21.
    Stumvoll M, Tschritter O, Fritsche A, Staiger H, Renn W, Weisser M, Machicao F, Haring H (2002) Association of the T-G polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 51:37–41PubMedGoogle Scholar
  22. 22.
    Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, Ouchi N, Kihara S, Kawamoto T, Sumitsuji S, Funahashi T, Matsuzawa Y (2002) Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 51:2325–2328PubMedGoogle Scholar
  23. 23.
    Menzaghi C, Ercolino T, Di Paola R, Berg AH, Warram JH, Scherer PE, Trischitta V, Doria A (2002) A haplotype at the adiponectin locus is associated with obesity and other features of the insulin resistance syndrome. Diabetes 51:2306–2312PubMedGoogle Scholar
  24. 24.
    Vasseur F, Helbecque N, Dina C, Lobbens S, Delannoy V, Gaget S, Boutin P, Vaxillaire M, Lepretre F, Dupont S, Hara K, Clement K, Bihain B, Kadowaki T, Froguel P (2002) Single-nucleotide polymorphism haplotypes in the both proximal promoter and exon 3 of the APM1 gene modulate adipocyte-secreted adiponectin hormone levels and contribute to the genetic risk for type 2 diabetes in French Caucasians. Hum Mol Genet 11:2607–2614CrossRefPubMedGoogle Scholar
  25. 25.
    Zietz B, Barth N, Scholmerich J, Schmitz G, Schaffler A (2001) Gly15Gly polymorphism within the human adipocyte-specific apM-1gene but not Tyr111His polymorphism is associated with higher levels of cholesterol and LDL-cholesterol in caucasian patients with type 2 diabetes. Exp Clin Endocrinol Diabetes 109:320–325PubMedGoogle Scholar
  26. 26.
    Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, Shimomura I, Hotta K, Kuriyama H, Kihara S, Nakamura T, Yamashita S, Funahashi T, Matsuzawa Y (2000) Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 24:861–868Google Scholar
  27. 27.
    Schaffler A, Barth N, Palitzsch KD, Drobnik W, Scholmerich J, Schmitz G (2000) Mutation analysis of the human adipocyte-specific apM-1 gene. Eur J Clin Invest 30:879–887PubMedGoogle Scholar
  28. 28.
    Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, Chen CL, Tai TY, Chuang LM (2001) Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86:3815–3819PubMedGoogle Scholar
  29. 29.
    Fingar DC, Birnbaum MJ (1994) Characterization of the mitogen-activated protein kinase/90-kilodalton ribosomal protein S6 kinase signaling pathway in 3T3–L1 adipocytes and its role in insulin-stimulated glucose transport. Endocrinology 134:728–735PubMedGoogle Scholar
  30. 30.
    Yan H, Yuan W, Velculescu VE, Vogelstein B, Kinzler KW (2002) Allelic variation in human gene expression. Science 297:1143CrossRefPubMedGoogle Scholar
  31. 31.
    Mendell JT, Dietz HC (2001) When the message goes awry: disease-producing mutations that influence mRNA content and performance. Cell 107:411–414PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2003

Authors and Affiliations

  • Wei-Shiung Yang
    • 1
    • 3
  • Pei-Ling Tsou
    • 2
  • Wei-Jei Lee
    • 5
  • Da-Lun Tseng
    • 3
  • Chi-Ling Chen
    • 4
  • Chi-Chung Peng
    • 1
  • Kuan-Ching Lee
    • 1
  • Mei-Ju Chen
    • 1
  • Chang-Jen Huang
    • 6
  • Tong-Yuan Tai
    • 1
  • Lee-Ming Chuang
    • 1
    • 3
  1. 1.Division of Endocrinology and Metabolism, Departments of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
  2. 2.Department of Clinical PathologyNational Taiwan University HospitalTaipeiTaiwan
  3. 3.Graduate Institute of Clinical MedicineNational Taiwan University Medical CollegeTaipeiTaiwan
  4. 4.Institute of EpidemiologyNational Taiwan UniversityTaipeiTaiwan
  5. 5.Department of SurgeryEn-Chu-Kong HospitalTaipei HsienTaiwan
  6. 6.Institute of Biological ChemistryAcademia SinicaTaipeiTaiwan

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