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A retrospective case control study identifies peripheral blood mononuclear cell albumin RNA expression as a biomarker for non-alcoholic fatty liver disease

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Abstract

Purpose

Non-alcoholic fatty liver disease (NAFLD) improves after bariatric surgery. The aim of this study was to determine whether peripheral blood mononuclear cell albumin gene expression was related to NAFLD and whether albumin (ALB) and alpha fetoprotein (AFP) expression could be detected in whole blood and visceral adipose tissue.

Methods

Using a retrospective case control study design, RNA isolated from peripheral blood mononuclear cells from patients prior to undergoing bariatric surgery was used for pooled microarray analysis. Quantitative polymerase chain reaction (QPCR) was used to analyze whole blood and visceral adipose tissue. Liver histology was obtained via intra-operative biopsy and clinical data extracted from the electronic health record.

Results

The albumin (ALB) gene was the second most up-regulated found in microarray analysis of peripheral blood mononuclear cell RNA from patients with hepatic lobular inflammation versus normal liver histology. Transcript levels of ALB were significantly different across those with normal (n = 50), steatosis (n = 50), lobular inflammation (n = 50), and peri-sinusoidal fibrosis (n = 50) liver histologies, with lobular inflammation 3.9 times higher than those with normal histology (p < 0.017). Albumin expression levels decreased in 11/13 patients in paired samples obtained prior to and at 1 year after Roux-en-Y gastric bypass surgery. ALB expression could be detected in 23 visceral adipose tissue samples obtained intra-operatively and in 18/19 available paired whole blood samples. No significant correlation was found between ALB expression in visceral adipose tissue and whole blood RNA samples. Alpha fetoprotein expression as a marker of early hepatocytic differentiation was detected in 17/17 available VAT RNA samples, but in only 2/17 whole blood RNA samples.

Conclusion

Albumin RNA expression from blood cells may serve as a biomarker of NAFLD. Albumin and alpha fetoprotein appear to be ubiquitously expressed in visceral adipose tissue in patients with extreme obesity.

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Acknowledgments

The authors would like to thank the patients and teams of the Temple and Geisinger Bariatric Surgery Programs for their willingness to participate in and support the research.

Funding

This work was supported by the National Institute of Diabetes and Digestive and Kidney Diseases (DK107735).

Author information

Authors and Affiliations

  1. Obesity Research Institute, Geisinger Clinic, Danville, PA, USA

    Xin Chu, G. Craig Wood, Weixing Shi & Christopher D. Still

  2. Department of Medical Genetics and Molecular Biochemistry, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA

    Kelsey Karasinski, Sean Donellan, Scott Kaniper & Glenn S. Gerhard

  3. Department of Surgery, Lewis Katz School of Medicine, Philadelphia, PA, 19140, USA

    Michael A. Edwards & Rohit Soans

Authors
  1. Xin Chu
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  2. Kelsey Karasinski
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  3. Sean Donellan
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  4. Scott Kaniper
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  5. G. Craig Wood
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  6. Weixing Shi
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  10. Glenn S. Gerhard
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Contributions

Study conception and design: MAE, RS, CDS, GSG. Acquisition of data: XC, KK, SD, SK, GCW, WS. Analysis and interpretation of data: XC, MAE, RS, CDS, GSG. Drafting of manuscript: GSG. Critical revision of manuscript: XC, MAE, RS, CDS, GSG.

Corresponding author

Correspondence to Glenn S. Gerhard.

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Conflicts of interest

The authors declare that they have no conflict of interest.

Statement of informed consent

Informed consent was obtained from all individual participants included in the study.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Institutional Review Boards of Geisinger Clinic and Temple University approved the research.

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Chu, X., Karasinski, K., Donellan, S. et al. A retrospective case control study identifies peripheral blood mononuclear cell albumin RNA expression as a biomarker for non-alcoholic fatty liver disease. Langenbecks Arch Surg 405, 165–172 (2020). https://doi.org/10.1007/s00423-019-01848-0

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  • DOI: https://doi.org/10.1007/s00423-019-01848-0

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