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Expression of Cytokine Signaling Genes in Morbidly Obese Patients with Non-Alcoholic Steatohepatitis and Hepatic Fibrosis

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Abstract

Background

White adipose tissue (WAT) from visceral adiposity plays an important role in the pathogenesis of non-alcoholic steatohepatitis (NASH). Development of NASH and its progression to fibrosis is partially due to cytokines and adipokines produced by WAT. The aim of this study was to assess the association of hepatic fibrosis and NASH by evaluating the intrinsic differences in the inflammatory cytokine signaling in the visceral adipose tissue obtained from morbidly obese patients.

Methods

We used targeted microarrays representing human genes involved in the inflammatory and fibrogenic reactions to profile visceral adipose samples of 15 well-matched NASH patients with and without fibrosis. Additionally, visceral adipose samples were subjected to real-time polymerase chain reaction profiling of 84 inflammations related genes.

Results

Eight genes (CCL2, CCL4, CCL18, CCR1, IL10RB, IL15RA, and LTB) were differentially expressed in NASH with fibrosis. Additionally, an overlapping but distinct list of the differentially expressed genes were found in NASH with type II diabetes (DM; IL8, BLR1, IL2RA, CD40LG, IL1RN, IL15RA, and CCL4) as compared to NASH without DM.

Conclusions

Inflammatory cytokines are differentially expressed in the adipose tissue of NASH with fibrosis, as well in NASH with DM. These findings point at the interaction of adipose inflammatory cytokines, DM, hepatic fibrosis in NASH, and its progression to cirrhosis and end-stage liver disease.

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Acknowledgments

This study was partly supported by the Liver Disease Outcomes Fund of the Center for Liver Diseases at Inova Fairfax Hospital and a Seed Grant from Inova Health System.

Financial Disclosure

None.

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Authors and Affiliations

  1. Center for Liver Diseases, Inova Fairfax Hospital, 3300 Gallows Road, Falls Church, VA, 22042, USA

    J. Michael Estep, Ancha Baranova, Arian Afendy & Zobair M. Younossi

  2. Center for the Study of Genomics in Liver Diseases, Molecular and Microbiology Department, George Mason University, Fairfax, VA, USA

    J. Michael Estep, Ancha Baranova, Vikas Chandhoke & Zobair M. Younossi

  3. Translational Research Institute, Inova Health System, Falls Church, VA, USA

    J. Michael Estep, Ancha Baranova, Noreen Hossain, Hazem Elariny, Kathy Ankrah, Arian Afendy, Vikas Chandhoke & Zobair M. Younossi

Authors
  1. J. Michael Estep
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  2. Ancha Baranova
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  3. Noreen Hossain
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  4. Hazem Elariny
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  5. Kathy Ankrah
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  6. Arian Afendy
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  7. Vikas Chandhoke
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  8. Zobair M. Younossi
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Corresponding author

Correspondence to Zobair M. Younossi.

Electronic Supplementary Material

Supplementary tables are located at the authors’ website (http://www.gmu.edu/departments/mmb/baranova/pages/focus-fibrosis-adipose.htm).

Supplementary Table 1

List of human genes profiled in adipose samples of NASH patients by microarray. Genes that were present only in microarray experiment, but not in RT-PCR experiment, are in italic (DOC 174 kb)

Supplementary Table 2

List of human genes profiled in adipose samples of NASH patients by RT-PCR. Genes that were present only in RT PCR experiment, but not in microarray experiment, are in italic (DOC 134 kb)

Supplementary Table 3

Cytokine signaling-related (CSR) genes expressed in the adipose tissue in each of the patients’ cohorts (DOC 109 kb)

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Estep, J.M., Baranova, A., Hossain, N. et al. Expression of Cytokine Signaling Genes in Morbidly Obese Patients with Non-Alcoholic Steatohepatitis and Hepatic Fibrosis. OBES SURG 19, 617–624 (2009). https://doi.org/10.1007/s11695-009-9814-x

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  • DOI: https://doi.org/10.1007/s11695-009-9814-x

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