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Adipocytokine expression associated with miRNA regulation and diagnosis of NASH in obese patients with NAFLD

Authors

  • J. Michael Estep,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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  • Zachary Goodman,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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  • Haveesh Sharma,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
    2. Center for the Study of Chronic Metabolic Diseases, George Mason University, Fairfax, VA, USA
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  • Elana Younossi,

    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
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  • Hazem Elarainy,

    1. Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA
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  • Ancha Baranova,

    1. Center for the Study of Chronic Metabolic Diseases, George Mason University, Fairfax, VA, USA
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  • Zobair Younossi

    Corresponding author
    1. Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA
    2. Center for the Study of Chronic Metabolic Diseases, George Mason University, Fairfax, VA, USA
    3. Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Falls Church, VA, USA
    • Correspondence

      Zobair M. Younossi, MD, MPH, FACG, FACP, AGAF, Department of Medicine, Inova Health System, Inova Fairfax Hospital, Beatty Center for Integrated Research, VCU-Inova Campus, 3300 Gallows Road, Falls Church, VA, 22042, USA

      Tel: +1 703 776 2540

      Fax: +1 703 776 4388

      e-mail: Zobair.Younossi@inova.org

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Abstract

Background & Aims

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with visceral adiposity. The secretion of adipocytokines from white adipose tissue (WAT) promoting necroinflammation, and/or fibrosis may play important roles in the pathogenesis of non-alcoholic steatohepatits (NASH). In a previous study, reduced expression of a number of miRNA species in WAT concomitant with histological diagnosis of NASH was successfully demonstrated. In this study, we measure the expression of several predicted miRNA regulatory targets relevant to NAFLD and NASH including mTOR, FAS, IL20, SEMA4C, ADAMTS6 and IL13RA. We then examine hepatic receptor expression by immunohistochemical staining and qPCR.

Methods

White adipose tissue was collected from 24 obese patients undergoing bariatric surgery with biopsy-proven NAFLD. Extracted total RNAs from the adipose tissue were reverse transcribed and profiled for gene expression by qPCR for specific individual mRNA targets defined after identification by any two of three of the major prediction services: miRanda, TarBase or PicTar. All liver biopsies were read by a singly hepatopathologist. The same liver tissue was used to stain for hepatic receptor expression for FASLG and IL20. Additionally, the same tissue was used for qPCR for FASLG and IL20.

Results

Increases in the expression of IL13RA, mTOR, IL20, SEMA4C and FAS were detected and negatively correlated with putative regulatory miRNA. Hepatic receptor expression for FAS and IL20 was noted to correlate with markers of inflammation and severity of NAFLD.

Conclusion

These data are consistent with the hypothesis that specific adipocytokines secreted by WAT will impact hepatic tissue and participate in the pathogenesis of NASH.

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