Skip to main content

Advertisement

SpringerLink
Log in

Hepatic Gene Networks in Morbidly Obese Patients With Nonalcoholic Fatty Liver Disease

  • Physiology Research
  • Published:
Obesity Surgery Aims and scope Submit manuscript

Abstract

Background

Genetic factors alter the risk for nonalcoholic fatty liver disease (NAFLD). We sought to identify NAFLD-associated genes and elucidate gene networks and pathways involved in the pathogenesis of NAFLD.

Methods

Quantitative global hepatic gene expression analysis was performed on 53 morbidly obese Caucasian subjects undergoing bariatric surgery (27 with NAFLD and 26 controls). After standardization of data, gene expression profiles were compared between patients with NAFLD and controls. The set of genes that significantly correlated with NAFLD was further analyzed by hierarchical clustering and ingenuity pathways analyses.

Results

There were 25,643 quantitative transcripts, of which 108 were significantly associated with NAFLD (p < 0.001). Canonical pathway analysis in the NAFLD-associated gene clusters showed that the hepatic fibrosis signaling was the most significant pathway in the up-regulated NAFLD gene cluster containing three (COL1A1, IL10, IGFBP3) significantly altered genes, whereas the endoplasmic reticulum stress and protein ubiquitination pathways were the most significant pathways in the down-regulated NAFLD gene cluster, with the first pathway containing one (HSPA5) and the second containing two (HSPA5, USP25) significantly altered genes. The four primary gene networks associated with NAFLD were involved in cell death, immunological disease, cellular movement, and lipid metabolism with several significantly altered “hub” genes in these networks.

Conclusions

This study reveals the canonical pathways and gene networks associated with NAFLD in morbidly obese Caucasians. The application of gene network analysis highlights the transcriptional relationships among NAFLD-associated genes and allows identification of hub genes that may represent high-priority candidates for NAFLD.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Schwimmer JB, Deutsch R, Kahen T, et al. Prevalence of fatty liver in children and adolescents. Pediatrics. 2006;118(4):1388–93.

    Article  PubMed  Google Scholar 

  2. Clark JM, Brancati FL, Diehl AM. The prevalence and etiology of elevated aminotransferase levels in the United States. Am J Gastroenterol. 2003;98(5):960–7.

    Article  CAS  PubMed  Google Scholar 

  3. Charlton M. Nonalcoholic fatty liver disease: a review of current understanding and future impact. Clin Gastroenterol Hepatol. 2004;2(12):1048–58.

    Article  PubMed  Google Scholar 

  4. Sanyal AJ. AGA technical review on nonalcoholic fatty liver disease. Gastroenterology. 2002;123(5):1705–25.

    Article  PubMed  Google Scholar 

  5. Brunt EM. Nonalcoholic steatohepatitis. Semin Liver Dis. 2004;24(1):3–20.

    Article  PubMed  Google Scholar 

  6. Matteoni CA, Younossi ZM, Gramlich T, et al. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology. 1999;116(6):1413–9.

    Article  CAS  PubMed  Google Scholar 

  7. Ekstedt M, Franzen LE, Mathiesen UL, et al. Long-term follow-up of patients with NAFLD and elevated liver enzymes. Hepatology. 2006;44(4):865–73.

    Article  CAS  PubMed  Google Scholar 

  8. Lazo M, Clark JM. The epidemiology of nonalcoholic fatty liver disease: a global perspective. Semin Liver Dis. 2008;28(4):339–50.

    Article  PubMed  Google Scholar 

  9. Browning JD, Horton JD. Molecular mediators of hepatic steatosis and liver injury. J Clin Invest. 2004;114(2):147–52.

    CAS  PubMed  Google Scholar 

  10. Dixon JB, Bhathal PS, O'Brien PE. Nonalcoholic fatty liver disease: predictors of nonalcoholic steatohepatitis and liver fibrosis in the severely obese. Gastroenterology. 2001;121(1):91–100.

    Article  CAS  PubMed  Google Scholar 

  11. Younossi ZM, Baranova A, Ziegler K, et al. A genomic and proteomic study of the spectrum of nonalcoholic fatty liver disease. Hepatology. 2005;42(3):665–74.

    Article  CAS  PubMed  Google Scholar 

  12. Struben VM, Hespenheide EE, Caldwell SH. Nonalcoholic steatohepatitis and cryptogenic cirrhosis within kindreds. Am J Med. 2000;108(1):9–13.

    Article  CAS  PubMed  Google Scholar 

  13. Willner IR, Waters B, Patil SR, et al. Ninety patients with nonalcoholic steatohepatitis: insulin resistance, familial tendency, and severity of disease. Am J Gastroenterol. 2001;96(10):2957–61.

    Article  CAS  PubMed  Google Scholar 

  14. Schwimmer JB, Celedon MA, Lavine JE, et al. Heritability of nonalcoholic fatty liver disease. Gastroenterology. 2009;136(5):1585–92.

    Article  PubMed  Google Scholar 

  15. Browning JD, Szczepaniak LS, Dobbins R, et al. Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity. Hepatology. 2004;40(6):1387–95.

    Article  PubMed  Google Scholar 

  16. Browning JD, Kumar KS, Saboorian MH, et al. Ethnic differences in the prevalence of cryptogenic cirrhosis. Am J Gastroenterol. 2004;99(2):292–8.

    Article  PubMed  Google Scholar 

  17. Miele L, Beale G, Patman G, et al. The Kruppel-like factor 6 genotype is associated with fibrosis in nonalcoholic fatty liver disease. Gastroenterology. 2008;135(1):282–91.

    Article  CAS  PubMed  Google Scholar 

  18. Romeo S, Kozlitina J, Xing C, et al. Genetic variation in PNPLA3 confers susceptibility to nonalcoholic fatty liver disease. Nat Genet. 2008;40(12):1461–5.

    Article  CAS  PubMed  Google Scholar 

  19. Yoneda M, Hotta K, Nozaki Y, et al. Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD). BMC Gastroenterol. 2008;8:27.

    Article  PubMed  Google Scholar 

  20. Sreekumar R, Rosado B, Rasmussen D, et al. Hepatic gene expression in histologically progressive nonalcoholic steatohepatitis. Hepatology. 2003;38(1):244–51.

    Article  CAS  PubMed  Google Scholar 

  21. Chiappini F, Barrier A, Saffroy R, et al. Exploration of global gene expression in human liver steatosis by high-density oligonucleotide microarray. Lab Invest. 2006;86(2):154–65.

    Article  CAS  PubMed  Google Scholar 

  22. Yoneda M, Endo H, Mawatari H, et al. Gene expression profiling of non-alcoholic steatohepatitis using gene set enrichment analysis. Hepatol Res. 2008;38(12):1204–12.

    CAS  PubMed  Google Scholar 

  23. Greco D, Kotronen A, Westerbacka J, et al. Gene expression in human NAFLD. Am J Physiol Gastrointest Liver Physiol. 2008;294(5):G1281–7.

    Article  CAS  PubMed  Google Scholar 

  24. Kleiner DE, Brunt EM, Van Natta M, et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology. 2005;41(6):1313–21.

    Article  PubMed  Google Scholar 

  25. Benjamini Y, Hochberg Y. Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc B. 1995;57:289–300.

    Google Scholar 

  26. Elam MB, Cowan Jr GS, Rooney RJ, et al. Hepatic gene expression in morbidly obese women: implications for disease susceptibility. Obesity (Silver Spring). 2009;17(8):1563–73.

    Article  CAS  Google Scholar 

  27. Maiti AK. Gene network analysis of oxidative stress-mediated drug sensitivity in resistant ovarian carcinoma cells. Pharmacogenomics J. 2010;10(2):94–104.

    Article  CAS  PubMed  Google Scholar 

  28. Goring HH, Curran JE, Johnson MP, et al. Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nat Genet. 2007;39(10):1208–16.

    Article  PubMed  Google Scholar 

  29. Eisen MB, Spellman PT, Brown PO, et al. Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci U S A. 1998;95(25):14863–8.

    Article  CAS  PubMed  Google Scholar 

  30. Furuhashi M, Hotamisligil GS. Fatty acid-binding proteins: role in metabolic diseases and potential as drug targets. Nat Rev Drug Discov. 2008;7(6):489–503.

    Article  CAS  PubMed  Google Scholar 

  31. Furuhashi M, Fucho R, Gorgun CZ, et al. Adipocyte/Macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice. J Clin Invest. 2008;118(7):2640–50.

    CAS  PubMed  Google Scholar 

  32. Tuncman G, Erbay E, Hom X, et al. A genetic variant at the fatty acid-binding protein aP2 locus reduces the risk for hypertriglyceridemia, type 2 diabetes, and cardiovascular disease. Proc Natl Acad Sci U S A. 2006;103(18):6970–5.

    Article  CAS  PubMed  Google Scholar 

  33. Maeda K, Cao H, Kono K, et al. Adipocyte/Macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes. Cell Metab. 2005;1(2):107–19.

    Article  CAS  PubMed  Google Scholar 

  34. Serra-Pages C, Medley QG, Tang M, et al. Liprins, a family of LAR transmembrane protein-tyrosine phosphatase-interacting proteins. J Biol Chem. 1998;273(25):15611–20.

    Article  CAS  PubMed  Google Scholar 

  35. Kriajevska M, Fischer-Larsen M, Moertz E, et al. Liprin beta 1, a member of the family of LAR transmembrane tyrosine phosphatase-interacting proteins, is a new target for the metastasis-associated protein S100A4 (Mts1). J Biol Chem. 2002;277(7):5229–35.

    Article  CAS  PubMed  Google Scholar 

  36. Yang JJ. Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest. Biochem Biophys Res Commun. 2002;297(1):105–10.

    Article  CAS  PubMed  Google Scholar 

  37. Jandhyala DM, Ahluwalia A, Obrig T, et al. ZAK: a MAP3Kinase that transduces Shiga toxin- and ricin-induced proinflammatory cytokine expression. Cell Microbiol. 2008;10(7):1468–77.

    Article  CAS  PubMed  Google Scholar 

  38. Cheng YC, Kuo WW, Wu HC, et al. ZAK induces MMP-2 activity via JNK/p38 signals and reduces MMP-9 activity by increasing TIMP-1/2 expression in H9c2 cardiomyoblast cells. Mol Cell Biochem. 2009;325(1–2):69–77.

    Article  CAS  PubMed  Google Scholar 

  39. Friedman SL. Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury. J Biol Chem. 2000;275(4):2247–50.

    Article  CAS  PubMed  Google Scholar 

  40. Yamaguchi M. Role of calcium-binding protein regucalcin in regenerating rat liver. J Gastroenterol Hepatol. 1998;13(Suppl):S106–12.

    CAS  PubMed  Google Scholar 

  41. Izumi T, Yamaguchi M. Overexpression of regucalcin suppresses cell death and apoptosis in cloned rat hepatoma H4-II-E cells induced by lipopolysaccharide, PD 98059, dibucaine, or Bay K 8644. J Cell Biochem. 2004;93(3):598–608.

    Article  CAS  PubMed  Google Scholar 

  42. Fukaya Y, Yamaguchi M. Overexpression of regucalcin suppresses cell death and apoptosis in cloned rat hepatoma H4-II-E cells induced by insulin or insulin-like growth factor-I. J Cell Biochem. 2005;96(1):145–54.

    Article  CAS  PubMed  Google Scholar 

  43. Matsubara M, Tanaka T, Terato H, et al. Action mechanism of human SMUG1 uracil-DNA glycosylase. Nucleic Acids Symp Ser (Oxf). 2005;49(49):295–6.

    Article  Google Scholar 

  44. Pettersen HS, Sundheim O, Gilljam KM, et al. Uracil-DNA glycosylases SMUG1 and UNG2 coordinate the initial steps of base excision repair by distinct mechanisms. Nucleic Acids Res. 2007;35(12):3879–92.

    Article  CAS  PubMed  Google Scholar 

  45. Seki S, Kitada T, Yamada T, et al. In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases. J Hepatol. 2002;37(1):56–62.

    Article  CAS  PubMed  Google Scholar 

  46. Khetani SR, Szulgit G, Del Rio JA, et al. Exploring interactions between rat hepatocytes and nonparenchymal cells using gene expression profiling. Hepatology. 2004;40(3):545–54.

    Article  CAS  PubMed  Google Scholar 

  47. Zhang Z, Li XJ, Liu Y, et al. Recombinant human decorin inhibits cell proliferation and downregulates TGF-beta1 production in hypertrophic scar fibroblasts. Burns. 2007;33(5):634–41.

    Article  PubMed  Google Scholar 

  48. Kalamajski S, Aspberg A, Lindblom K, et al. Asporin competes with decorin for collagen binding, binds calcium and promotes osteoblast collagen mineralization. Biochem J. 2009;423(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  49. Chen AA, Khetani SR, Lee S, et al. Modulation of hepatocyte phenotype in vitro via chemomechanical tuning of polyelectrolyte multilayers. Biomaterials. 2009;30(6):1113–20.

    Article  CAS  PubMed  Google Scholar 

  50. Wang Y, Lu C, Wei H, et al. Hepatopoietin interacts directly with COP9 signalosome and regulates AP-1 activity. FEBS Lett. 2004;572(1–3):85–91.

    Article  CAS  PubMed  Google Scholar 

  51. Pearce C, Hayden RE, Bunce CM, et al. Analysis of the role of COP9 signalosome (CSN) subunits in K562; the first link between CSN and autophagy. BMC Cell Biol. 2009;10:31.

    Article  PubMed  Google Scholar 

  52. Kato JY, Yoneda-Kato N. Mammalian COP9 signalosome. Genes Cells. 2009;14(11):1209–25.

    Article  CAS  PubMed  Google Scholar 

  53. Laplante JM, O'Rourke F, Lu X, et al. Cloning of human Ca2+ homoeostasis endoplasmic reticulum protein (CHERP): regulated expression of antisense cDNA depletes CHERP, inhibits intracellular Ca2+ mobilization and decreases cell proliferation. Biochem J. 2000;348(Pt 1):189–99.

    Article  CAS  PubMed  Google Scholar 

  54. Vallee RB, Williams JC, Varma D, et al. Dynein: an ancient motor protein involved in multiple modes of transport. J Neurobiol. 2004;58(2):189–200.

    Article  CAS  PubMed  Google Scholar 

  55. Gennerich A, Vale RD. Walking the walk: how kinesin and dynein coordinate their steps. Curr Opin Cell Biol. 2009;21(1):59–67.

    Article  CAS  PubMed  Google Scholar 

  56. Feldstein AE, Canbay A, Angulo P, et al. Hepatocyte apoptosis and fas expression are prominent features of human nonalcoholic steatohepatitis. Gastroenterology. 2003;125(2):437–43.

    Article  PubMed  Google Scholar 

  57. Malhi H, Bronk SF, Werneburg NW, et al. Free fatty acids induce JNK-dependent hepatocyte lipoapoptosis. J Biol Chem. 2006;281(17):12093–101.

    Article  CAS  PubMed  Google Scholar 

  58. Li Z, Oben JA, Yang S, et al. Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis. Hepatology. 2004;40(2):434–41.

    Article  CAS  PubMed  Google Scholar 

  59. Li Z, Soloski MJ, Diehl AM. Dietary factors alter hepatic innate immune system in mice with nonalcoholic fatty liver disease. Hepatology. 2005;42(4):880–5.

    Article  CAS  PubMed  Google Scholar 

  60. den Boer MA, Voshol PJ, Schroder-van der Elst JP, et al. Endogenous interleukin-10 protects against hepatic steatosis but does not improve insulin sensitivity during high-fat feeding in mice. Endocrinology. 2006;147(10):4553–8.

    Article  Google Scholar 

  61. Chan SS, Schedlich LJ, Twigg SM, et al. Inhibition of adipocyte differentiation by insulin-like growth factor-binding protein-3. Am J Physiol Endocrinol Metab. 2009;296(4):E654–63.

    Article  CAS  PubMed  Google Scholar 

  62. Silha JV, Gui Y, Murphy LJ. Impaired glucose homeostasis in insulin-like growth factor-binding protein-3-transgenic mice. Am J Physiol Endocrinol Metab. 2002;283(5):E937–45.

    CAS  PubMed  Google Scholar 

  63. Chan SS, Twigg SM, Firth SM, et al. Insulin-like growth factor binding protein-3 leads to insulin resistance in adipocytes. J Clin Endocrinol Metab. 2005;90(12):6588–95.

    Article  CAS  PubMed  Google Scholar 

  64. Oh Y, Muller HL, Lamson G, et al. Insulin-like growth factor (IGF)-independent action of IGF-binding protein-3 in Hs578T human breast cancer cells. Cell surface binding and growth inhibition. J Biol Chem. 1993;268(20):14964–71.

    CAS  PubMed  Google Scholar 

  65. Rajah R, Valentinis B, Cohen P. Insulin-like growth factor (IGF)-binding protein-3 induces apoptosis and mediates the effects of transforming growth factor-beta1 on programmed cell death through a p53- and IGF-independent mechanism. J Biol Chem. 1997;272(18):12181–8.

    Article  CAS  PubMed  Google Scholar 

  66. Zhang K, Kaufman RJ. From endoplasmic-reticulum stress to the inflammatory response. Nature. 2008;454(7203):455–62.

    Article  CAS  PubMed  Google Scholar 

  67. Hirsch C, Gauss R, Horn SC, et al. The ubiquitylation machinery of the endoplasmic reticulum. Nature. 2009;458(7237):453–60.

    Article  CAS  PubMed  Google Scholar 

  68. Wei Y, Wang D, Pagliassotti MJ. Saturated fatty acid-mediated endoplasmic reticulum stress and apoptosis are augmented by trans-10, cis-12-conjugated linoleic acid in liver cells. Mol Cell Biochem. 2007;303(1–2):105–13.

    Article  CAS  PubMed  Google Scholar 

  69. Puri P, Mirshahi F, Cheung O, et al. Activation and dysregulation of the unfolded protein response in nonalcoholic fatty liver disease. Gastroenterology. 2008;134(2):568–76.

    Article  CAS  PubMed  Google Scholar 

  70. Ni M, Lee AS. ER chaperones in mammalian development and human diseases. FEBS Lett. 2007;581(19):3641–51.

    Article  CAS  PubMed  Google Scholar 

  71. Zhang L, Lai E, Teodoro T, et al. GRP78, but Not Protein-disulfide isomerase, partially reverses hyperglycemia-induced inhibition of insulin synthesis and secretion in pancreatic {beta}-cells. J Biol Chem. 2009;284(8):5289–98.

    Article  CAS  PubMed  Google Scholar 

  72. Kammoun HL, Chabanon H, Hainault I, et al. GRP78 expression inhibits insulin and ER stress-induced SREBP-1c activation and reduces hepatic steatosis in mice. J Clin Invest. 2009;119(5):1201–15.

    Article  CAS  PubMed  Google Scholar 

  73. Valero R, Marfany G, Gonzalez-Angulo O, et al. USP25, a novel gene encoding a deubiquitinating enzyme, is located in the gene-poor region 21q11.2. Genomics. 1999;62(3):395–405.

    Article  CAS  PubMed  Google Scholar 

  74. Valero R, Bayes M, Francisca Sanchez-Font M, et al. Characterization of alternatively spliced products and tissue-specific isoforms of USP28 and USP25. Genome Biol. 2001;2(10):RESEARCH0043.

    Article  CAS  PubMed  Google Scholar 

  75. Carlson MR, Zhang B, Fang Z, et al. Gene connectivity, function, and sequence conservation: predictions from modular yeast co-expression networks. BMC Genomics. 2006;7:40.

    Article  PubMed  Google Scholar 

  76. MacLennan NK, Dong J, Aten JE, et al. Weighted gene co-expression network analysis identifies biomarkers in glycerol kinase deficient mice. Mol Genet Metab. 2009;98(1–2):203–14.

    Article  CAS  PubMed  Google Scholar 

  77. Horvath S, Zhang B, Carlson M, et al. Analysis of oncogenic signaling networks in glioblastoma identifies ASPM as a molecular target. Proc Natl Acad Sci U S A. 2006;103(46):17402–7.

    Article  CAS  PubMed  Google Scholar 

  78. Saris CG, Horvath S, van Vught PW, et al. Weighted gene co-expression network analysis of the peripheral blood from amyotrophic lateral sclerosis patients. BMC Genomics. 2009;10:405.

    Article  PubMed  Google Scholar 

  79. Sharma MR, Polavarapu R, Roseman D, et al. Transcriptional networks in a rat model for nonalcoholic fatty liver disease: a microarray analysis. Exp Mol Pathol. 2006;81(3):202–10.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Division of Gastroenterology and Hepatology, Medical College of Wisconsin, 9200 W. Wisconsin Ave, Milwaukee, WI, 53212, USA

    Samer Gawrieh

  2. Division of General Internal Medicine, Medical College of Wisconsin, Milwaukee, WI, USA

    Russell Wilke

  3. Division of Endocrinology, Medical College of Wisconsin, Milwaukee, WI, USA

    Bassem Makladi & Ahmed H. Kissebah

  4. Zablocki VA Medical Center, Milwaukee, WI, USA

    Samer Gawrieh

  5. Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Tesfaye M. Baye, Regina Cole, Russell Wilke, Ahmed H. Kissebah & Michael Olivier

  6. Biotechnology and Bioengineering Center, Medical College of Wisconsin, Milwaukee, WI, USA

    Tesfaye M. Baye, Regina Cole & Michael Olivier

  7. Department of Genetics, Southwest Foundation for Biomedical Research, San Antonio, TX, USA

    Melanie Carless, Joanne Curran, Thomas D. Dyer, Jac Charlesworth & John Blangero

  8. Department of Surgery, Medical College of Wisconsin, Milwaukee, WI, USA

    James Wallace & Deborah Andris

  9. Department of Pathology, Medical College of Wisconsin, Milwaukee, WI, USA

    Richard Komorowski

  10. Laboratory of Pathology, National Cancer Institute, Bethesda, MD, USA

    David E. Kleiner

  11. Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA

    Michael Charlton

  12. Department of Physiology, Medical College of Wisconsin, Milwaukee, WI, USA

    Michael Olivier

Authors
  1. Samer Gawrieh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tesfaye M. Baye
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Melanie Carless
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. James Wallace
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard Komorowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. David E. Kleiner
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Deborah Andris
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Bassem Makladi
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Regina Cole
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael Charlton
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Joanne Curran
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Thomas D. Dyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Jac Charlesworth
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Russell Wilke
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. John Blangero
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Ahmed H. Kissebah
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Michael Olivier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Samer Gawrieh.

Additional information

This work was funded by a grant from the Biotechnology and Bioengineering Center of the Medical College of Wisconsin (SG and MO) and grant HL74168 from the Heart, Lung, and Blood Institute of the National Institutes of Health (MO).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gawrieh, S., Baye, T.M., Carless, M. et al. Hepatic Gene Networks in Morbidly Obese Patients With Nonalcoholic Fatty Liver Disease. OBES SURG 20, 1698–1709 (2010). https://doi.org/10.1007/s11695-010-0171-6

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11695-010-0171-6

Keywords

Search

Navigation