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Adipose tissue gene expression and metabolic health of obese adults

International Journal of Obesity volume 39, pages 869–873 (2015)Cite this article

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Abstract

Obese subjects with a similar body mass index (BMI) exhibit substantial heterogeneity in gluco- and cardiometabolic heath phenotypes. However, defining genes that underlie the heterogeneity of metabolic features among obese individuals and determining metabolically healthy and unhealthy phenotypes remain challenging. We conducted unsupervised hierarchical clustering analysis of subcutaneous adipose tissue transcripts from 30 obese men and women ⩾40 years old. Despite similar BMIs in all subjects, we found two distinct subgroups, one metabolically healthy (group 1) and one metabolically unhealthy (group 2). Subjects in group 2 showed significantly higher total cholesterol (P=0.005), low-density lipoprotein cholesterol (P=0.006), 2-h insulin during oral glucose tolerance test (P=0.015) and lower insulin sensitivity (SI, P=0.029) compared with group 1. We identified significant upregulation of 141 genes (for example, MMP9 and SPP1) and downregulation of 17 genes (for example, NDRG4 and GINS3) in group 2 subjects. Intriguingly, these differentially expressed transcripts were enriched for genes involved in cardiovascular disease-related processes (P=2.81 × 10−11–3.74 × 10−02) and pathways involved in immune and inflammatory response (P=8.32 × 10−5–0.04). Two downregulated genes, NDRG4 and GINS3, have been located in a genomic interval associated with cardiac repolarization in published GWASs and zebra fish knockout models. Our study provides evidence that perturbations in the adipose tissue gene expression network are important in defining metabolic health in obese subjects.

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References

  1. Ahima RS, Lazar MA . Physiology. The health risk of obesity—better metrics imperative. Science 2013; 341: 856–858.

    Article  CAS  Google Scholar 

  2. Bluher M . The distinction of metabolically 'healthy' from 'unhealthy' obese individuals. Curr Opin Lipidol 2010; 21: 38–43.

    Article  Google Scholar 

  3. Phillips CM . Metabolically healthy obesity: definitions, determinants and clinical implications. Rev Endocr Metab Disord 2013; 14: 219–227.

    Article  CAS  Google Scholar 

  4. Tchkonia T, Thomou T, Zhu Y, Karagiannides I, Pothoulakis C, Jensen MD et al. Mechanisms and metabolic implications of regional differences among fat depots. Cell Metab 2013; 17: 644–656.

    Article  CAS  Google Scholar 

  5. Jo J, Gavrilova O, Pack S, Jou W, Mullen S, Sumner AE et al. Hypertrophy and/or hyperplasia: dynamics of adipose tissue growth. PLoS Comput Biol 2009; 5: e1000324.

    Article  Google Scholar 

  6. Despres JP, Lemieux I . Abdominal obesity and metabolic syndrome. Nature 2006; 444: 881–887.

    Article  CAS  Google Scholar 

  7. Van Gaal LF, Mertens IL, De Block CE . Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: 875–880.

    Article  CAS  Google Scholar 

  8. Das SK, Sharma NK, Hasstedt SJ, Mondal AK, Ma L, Langberg KA et al. An integrative genomics approach identifies activation of thioredoxin/thioredoxin reductase-1-mediated oxidative stress defense pathway and inhibition of angiogenesis in obese nondiabetic human subjects. J Clin Endocrinol Metab 2011; 96: E1308–E1313.

    Article  CAS  Google Scholar 

  9. Elbein SC, Kern PA, Rasouli N, Yao-Borengasser A, Sharma NK, Das SK . Global gene expression profiles of subcutaneous adipose and muscle from glucose-tolerant, insulin-sensitive, and insulin-resistant individuals matched for BMI. Diabetes 2011; 60: 1019–1029.

    Article  CAS  Google Scholar 

  10. Keller MP, Attie AD . Physiological insights gained from gene expression analysis in obesity and diabetes. Annu Rev Nutr 2010; 30: 341–364.

    Article  CAS  Google Scholar 

  11. Qatanani M, Tan Y, Dobrin R, Greenawalt DM, Hu G, Zhao W et al. Inverse regulation of inflammation and mitochondrial function in adipose tissue defines extreme insulin sensitivity in morbidly obese patients. Diabetes 2013; 62: 855–863.

    Article  CAS  Google Scholar 

  12. Sharma NK, Langberg KA, Mondal AK, Das SK . Phospholipid biosynthesis genes and susceptibility to obesity: analysis of expression and polymorphisms. PLoS One 2013; 8: e65303.

    Article  CAS  Google Scholar 

  13. Caraux G, Pinloche S . PermutMatrix: a graphical environment to arrange gene expression profiles in optimal linear order. Bioinformatics 2005; 21: 1280–1281.

    Article  CAS  Google Scholar 

  14. Tusher VG, Tibshirani R, Chu G . Significance analysis of microarrays applied to the ionizing radiation response. Proc Natl Acad Sci USA 2001; 98: 5116–5121.

    Article  CAS  Google Scholar 

  15. Huang dW, Sherman BT, Lempicki RA . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc 2009; 4: 44–57.

    Article  CAS  Google Scholar 

  16. Guilherme A, Virbasius JV, Puri V, Czech MP . Adipocyte dysfunctions linking obesity to insulin resistance and type 2 diabetes. Nat Rev Mol Cell Biol 2008; 9: 367–377.

    Article  CAS  Google Scholar 

  17. Newton-Cheh C, Eijgelsheim M, Rice KM, de Bakker PI, Yin X, Estrada K et al. Common variants at ten loci influence QT interval duration in the QTGEN Study. Nat Genet 2009; 41: 399–406.

    Article  CAS  Google Scholar 

  18. Pfeufer A, Sanna S, Arking DE, Muller M, Gateva V, Fuchsberger C et al. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nat Genet 2009; 41: 407–414.

    Article  CAS  Google Scholar 

  19. Qu X, Jia H, Garrity DM, Tompkins K, Batts L, Appel B et al. Ndrg4 is required for normal myocyte proliferation during early cardiac development in zebrafish. Dev Biol 2008; 317: 486–496.

    Article  CAS  Google Scholar 

  20. Milan DJ, Kim AM, Winterfield JR, Jones IL, Pfeufer A, Sanna S et al. Drug-sensitized zebrafish screen identifies multiple genes, including GINS3, as regulators of myocardial repolarization. Circulation 2009; 120: 553–559.

    Article  Google Scholar 

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Acknowledgements

This work was supported by grant R01 DK039311 and R01 DK090111 from the National Institutes of Health/NIDDK. We thank the Clinical Research Center staff of University of Arkansas for Medical Sciences for their outstanding support in the physiologic studies and assistance with data management. We thank Prof Siqun Zheng, Director, and the technical staff of the Center for Human Genomics, Wake Forest School of Medicine, especially Ms Shelly Smith and Dr Ge Li for their extensive support in gene expression analysis. We also thank Ethel Kouba (Internal Medicine, Endocrinology) and Karen Klein (Biomedical Research Services and Administration) for critical reading and editing of our manuscript.

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  1. Department of Internal Medicine, Section on Endocrinology and Metabolism, Wake Forest School of Medicine, Winston-Salem, NC, USA,

    S K Das, L Ma & N K Sharma

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  1. S K Das
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Correspondence to S K Das.

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Supplementary Information accompanies this paper on International Journal of Obesity website

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Das, S., Ma, L. & Sharma, N. Adipose tissue gene expression and metabolic health of obese adults. Int J Obes 39, 869–873 (2015). https://doi.org/10.1038/ijo.2014.210

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