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Genome-wide scan of resistin mRNA expression in omental adipose tissue of baboons

International Journal of Obesity volume 29, pages 406–412 (2005)Cite this article

Abstract

INTRODUCTION:

The hormone resistin was recently discovered in adipose tissue of mice. Functional tests suggest a role for resistin in the regulation of insulin sensitivity. However, human studies have reported controversial results on the metabolic function of this hormone.

METHODS:

A 1 g omental adipose tissue biopsy was obtained from 404 adult baboons. Resistin mRNA expression was assayed by real-time, quantitative RT-PCR, and univariate and bivariate quantitative genetic analyses were performed, via the variance decomposition approach. A genome scan analysis was conducted using resistin mRNA abundance in omental adipose tissue as a quantitative phenotype.

RESULTS:

A significant heritability of h2=0.23 (P=0.003) was found for resistin mRNA abundance in omental adipose tissue. A genome scan detected a quantitative trait locus for resistin expression with an LOD score of 3.8, in the region between markers D19S431 and D19S714, corresponding to human chromosome 19 p13. This chromosomal region contains genes related to insulin resistance phenotypes, such as resistin, insulin receptor, angiopoietin-like 4 protein and LDL receptor.

CONCLUSIONS:

Individual variation in resistin mRNA expression has a significant genetic component, and a gene or genes on chromosome 19p13 may regulate resistin mRNA levels in baboon omental adipose tissue.

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References

  1. Viengchareun S, Zennaro MC, Pscual-Le Tallec L, Lombes M . Brown adipocytes are novel sites of expression and regulation of resistin and adiponectin. FEBS Lett 2002; 532: 345–350.

    Article  CAS  Google Scholar 

  2. Steppan C, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, Lazar MA . The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312.

    Article  CAS  Google Scholar 

  3. Patel L, Buckels A, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, Macphee CH, Smith SA . Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochem Biophys Res Commun 2003; 300: 472–476.

    Article  CAS  Google Scholar 

  4. Moore GB, Chapman H, Holder JC, Lister CA, Piercy V, Smith SA, Clapham JC . Differential regulation of adipocytokine mRNAs by rosiglitazone in db/db mice. Biochem Biophys Res Commun 2001; 286: 735–741.

    Article  CAS  Google Scholar 

  5. Way JM, Gorgun CZ, Tong Q, Uysal KT, Harrington WW, Oliver Jr WR, Willson TM, Kliewer SA, Hotamisligil GS . Adipose tissue resistin expression is severely suppressed in obesity and stimulated by perosixome proliferator-activated receptor γ agonists. J Biol Chem 2001; 276: 25651–25653.

    Article  CAS  Google Scholar 

  6. Janke J, Engeli S, Gorzelniak K, Luft F, Sharma A . Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res 2002; 10: 1–5.

    Article  CAS  Google Scholar 

  7. Nagaev I, Smith U . Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 2001; 285: 561–564.

    Article  CAS  Google Scholar 

  8. Zhang J, Qin Y, Zheng X, Qiu J, Gong L, Mao H, Jia W, Guo J . The relationship between human serum resistin level and body fat content, plasma glucose as well as blood pressure. Zhonghua Yi Xue Za Zhi 2002; 82: 1609–1612.

    CAS  PubMed  Google Scholar 

  9. Yannakoulia M, Yiannakouris N, Bluher S, Mtalas AL, Klimis D, Mantzoros C . Body fat mass and macronutrient intake in relation to circulatin soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metabol 2003; 88: 1730–1736.

    Article  CAS  Google Scholar 

  10. Fain J, Cheema P, Bahout S, Hiler M . Resistin release by human adipose tissue explants in primary culture. Biochem Biophys Res Commun 2003; 300: 674–678.

    Article  CAS  Google Scholar 

  11. McTernan P, Mc Ternan C, Chetty R, Jenner K, Fisher FM, Lauer M, Crocker J, Barnett A, Kumar S . Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 2002; 87: 2407–2410.

    Article  CAS  Google Scholar 

  12. Mc Ternan CL, Mc Ternan PG, Harte AL, Levick PL, Barnett AH, Kumar S . Resistin, central obesity and type 2 diabetes. Lancet 2002; 359: 46–47.

    Article  CAS  Google Scholar 

  13. Festa A, D’Agostino Jr R, Howard G, Mykkanen L, Tracy RP, Haffner SM . Chronic subclinical inflammation as part of the insulin resistance syndrome: the Insulin Resistance Atherosclerosis study. Circulation 2000; 102: 42–47.

    Article  CAS  Google Scholar 

  14. Ford ES . The metabolic syndrome and C-reactive protein, fibrinogen, and leukocyte count: findings from the Third National Health and Nutrition Examination Survey. Atherosclerosis 2003; 168: 351–358.

    Article  CAS  Google Scholar 

  15. Yudkin JS, Stehouwer CD, Emels JJ, Coppack SW . C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from the adipose tissue? Arteioscler Thromb Vasc Biol 1999; 19: 972–978.

    Article  CAS  Google Scholar 

  16. Rifai N, Ridker PM . Inflammatory markers and coronary heart disease. Curr Opin Lipidol 2002; 13: 383–389.

    Article  CAS  Google Scholar 

  17. Stumvoll M, Haring H . Resistin and adiponectin-of mice and men. Obes Res 2002; 10: 1197–1198.

    Article  Google Scholar 

  18. Wang H, Chu WS, Hemphill C, Elbein SC . Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians. J Clin Endocrinol Metab 2002; 87: 2520–2524.

    Article  CAS  Google Scholar 

  19. Cao H, Hegele RA . Single nucleotide polymorphisms of the resistin (RSTN) gene. J Hum Genet 2001; 46: 553–555.

    Article  CAS  Google Scholar 

  20. Comuzzie AG . The emerging pattern of the genetic contribution to human obesity. Best Pract Res Clin Endocrinol Metab 2002; 16: 611–621.

    Article  Google Scholar 

  21. Clement K, Boutin P, Froguel P . Genetics of obesity. Am J Pharmacogenomics 2002; 2: 177–187.

    Article  CAS  Google Scholar 

  22. Chagnon YC, Rankinen T, Snyder EE, Weisnagel SJ, Perusse L, Bouchard C . The human obesity gene map: the 2002 update. Obes Res 2003; 11: 313–367.

    Article  CAS  Google Scholar 

  23. Cole SA, Martin LJ, Peebles KW, Leland MM, Rice K, VandeBerg JL, Blangero J, Comuzzie AG . Genetics of leptin expression in baboons. Int J Obes Relat Metab Disord 2003; 27: 778–783.

    Article  CAS  Google Scholar 

  24. Lewis DS, Bertrand HA, McMahan CA, McGill Jr HC, Carey KD, Masoro EJ . Preweaning food intake influences the adiposity of young adult baboons. J Clin Invest 1986; 78: 899–905.

    Article  CAS  Google Scholar 

  25. Tejero ME, Freeland-Graves, Proffitt JM, Peebles KW, Cole SA, Comuzzie AG . Adiponectin, but not resistin expression in monocytes is associated with insulin resistance in baboons. Obes Res 2004; 12: 871–877.

    Article  CAS  Google Scholar 

  26. Rogers J, Witte SM, Kammerer CM, Hixson JE, Mac Cluer JW . Linkage mapping in papio baboons: conservation of a syntenic group of six markers on human chromosome 1. Genomics 1995; 28: 251–254.

    Article  CAS  Google Scholar 

  27. Rogers J, Mahaney MC, Witte SM, Nair S, Newman D, Wedel S, Rodriguez LA, Rice KS, Slifer SH, Perelygin A, Slifer M, Palladino-Negro P, Newman T, Chambers K, Joslyn G, Parry P, Morin PA . A genetic linkage map of the baboon (papio hamadyas) genome based on human microsatellite polymorphisms. Genomics 2000; 67: 237–247.

    Article  CAS  Google Scholar 

  28. Almasy L, Blangero J . Multipoint quantitative-trait linkage analysis in general pedigrees. Am J Human Genet 1998; 62: 1198–1211.

    Article  CAS  Google Scholar 

  29. Self SG, Liang KY . Asymptotic properties of maximum likelihood ratio test under nonstandard conditions. J Am Stat Assoc 1987; 82: 605–610.

    Article  Google Scholar 

  30. Hopper JL, Mathews JD . Extensions to multivariate normal models for pedigree analysis. Ann Hum Genet 1982; 46: 373–383.

    Article  CAS  Google Scholar 

  31. Rice T, Rankinen T, Province MA, Chagnon YC, Perusse L, Borecki IB, Bouchard C, Rao DC . Genome-wide linkage analysis of systolic and diastolic blood pressure: the Quebec Family Study. Circulation 2000; 102: 1956–1963.

    Article  CAS  Google Scholar 

  32. Cooper RS, Luke A, Zhu X, Kan D, Adeyemo A, Rotimi C, Bouzerki N, Ward R, Rorimi C . Genome scan among Nigerians linking blood pressure to chromosomes 2,3 and 19. Hypertension 2002; 40: 629–633.

    Article  CAS  Google Scholar 

  33. Yang YS, Song HD, Shi WJ, Hu RM, Han ZG, Chen JL . Chromosome localization analysis of genes strongly expressed in human visceral adipose tissue. Endocrine 2002; 18: 57–66.

    Article  CAS  Google Scholar 

  34. Engert JC, Vohl MC, Williams SM, Lepage P, Loredo-Osti JC, Faith J, Dore C, Renaud Y, Burtt NP, Villeneuve A, Hirschhorn JN, Altshuler D, Groop LC, Despres JP, Gaudet D, Hudson TJ . 5′ flanking variants of resistin are associated with obesity. Diabetes 2002; 51: 1629–1634.

    Article  CAS  Google Scholar 

  35. Ma X, Warram JH, Trischitta V, Doria A . Genetic variants at the resistin locus and risk of type 2 diabetes in Caucasians. J Clin Endocrinol Metab 2002; 87: 4407–4410.

    Article  CAS  Google Scholar 

  36. Smith SR, Bai F, Charbonneau Ch, Janderova L, Argyropoulos G . A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 2003; 52: 1611–1618.

    Article  CAS  Google Scholar 

  37. Zee RYL, Lou Y, Morris BJ . Insertion variant in intron 9, but not microsatellite in intron 2, of the insulin receptor gene is associated with essential hypertension. J Hypertens 1994; 12 (Suppl 7): S13–S22.

    CAS  Google Scholar 

  38. Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE, Spelgelman BM . Peroxisome proliferator-activated g target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol 2000; 20: 5343–5349.

    Article  CAS  Google Scholar 

  39. Griffiths LR, Nyholt DR, Curtain RP, Gaffney PT, Morris BJ . Cross-sectional study of a microsatellite marker in the low density lipoprotein receptor gene in obese normotensives. Clin Exp Pharmacol Physiol 1995; 22: 496–498.

    Article  CAS  Google Scholar 

  40. Zee RY, Schrader AP, Robinson BG, Griffiths LR, Morris BJ . Association of HincII RFLP of low density lipoprotein receptor gene with obesity in essential hypertensives. Clin Genet 1995; 47: 118–121.

    Article  CAS  Google Scholar 

  41. Jove M, Planavila A, Cabrero A, Novell F, Ros E, Zambon D, Laguna JC, Carrera MV . Reductions in plasma cholesterol levels after fenofibrate treatment are negatively correlated with resistin expression human adipose tissue. Metabolism 2003; 52: 351–355.

    Article  CAS  Google Scholar 

  42. Groop L . Genetics of the metabolic syndrome. Br J Nutr 2000; 83 (Suppl 1): S39–S48.

    CAS  PubMed  Google Scholar 

  43. Nogueiras R, Gualillo O, Caminos E, Casanueva FF, Dieguez C . Regulation of resistin by gonadal, tyroid hormone, and nutritional status. Obes Res 2003; 11: 408–414.

    Article  CAS  Google Scholar 

  44. Comuzzie AG, Blangero J, Mahaney M, Haffner SM, Mitchell BD, Stern MP, Mac Cluer JW . Genetic and environmental correlations among hormone levels and measures of body fat accumulation and topography. J Clin Endocrinol Metab 1996; 81: 597–600.

    CAS  PubMed  Google Scholar 

  45. Matthews DR, Hosker JP, Rudensky AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  46. Savage D, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, O’Rahilly S . Resistin/Fizz3 expression in relation to obesity and peroxisome proliferators-activated receptor-ã action in humans. Diabetes 2001; 50: 2199–2202.

    Article  CAS  Google Scholar 

  47. Tejero ME, Proffitt JM, Cole SA, Cai G, Freeland-Graves JH, Peebles KW, Comuzzie AG . Association between circulating levels of pro-inflammatory cytokines and the expression of adiponectin, resistin and GLUT4 in omental adipose tissue of baboons. Rev Investig Clin 2004, in review.

  48. Silha JV, Krsek M, Skrha JV, Sucharda P, Nyomba BLG, Murphy L . Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003; 149: 331–335.

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by grants NIH grants HL28972 and P51RR3986. ME Tejero was supported by a Fulbright-CONACyT, Mexico grant.

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Authors and Affiliations

  1. Division of Nutritional Sciences, The University of Texas at Austin, Austin, TX, USA

    M E Tejero, G Cai & J H Freeland-Graves

  2. Department of Genetics at the Southwest Foundation for Biomedical Sciences, San Antonio, TX, USA

    M E Tejero, S A Cole, G Cai, K W Peebles, L A Cox, M C Mahaney, J Rogers, J L VandeBerg, J Blangero & A G Comuzzie

  3. Southwest National Primate Center, San Antonio, TX, USA

    J Rogers & J L VandeBerg

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  1. M E Tejero
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  2. S A Cole
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Correspondence to A G Comuzzie.

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Tejero, M., Cole, S., Cai, G. et al. Genome-wide scan of resistin mRNA expression in omental adipose tissue of baboons. Int J Obes 29, 406–412 (2005). https://doi.org/10.1038/sj.ijo.0802699

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