Distinct Hepatic Gene‐Expression Patterns of NAFLD in Patients With Obesity
Name
Hepatology Communications - 2021 - Subudhi - Distinct Hepatic Gene%u2010Expression Patterns of NAFLD in Patients With Obesity.pdf
Description
Published version
Size
936.26 KB
Format
Adobe PDF
Checksum (MD5)
058a3fdb43e9bddb92859eb8304cd595
Author(s)
Subudhi, Sonu
Drescher, Hannah K
Dichtel, Laura E
Bartsch, Lea M
Chung, Raymond T
Hutter, Matthew M
Gee, Denise W
Meireles, Ozanan R
Witkowski, Elan R
Gelrud, Louis
Date Issued
2022
Journal
Hepatology Communications
Publisher
Wiley
Citation
Subudhi, Sonu, Drescher, Hannah K, Dichtel, Laura E, Bartsch, Lea M, Chung, Raymond T et al. 2022. "Distinct Hepatic Gene‐Expression Patterns of NAFLD in Patients With Obesity." Hepatology Communications, 6 (1).
Version
Final published version
Abstract
Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene-expression patterns associated with different patterns of liver injury in a high-risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes: normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1-4 (NASH F1-F4). One hundred twenty-five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma-interferon-inducible lysosomal thiol reductase (IFI30) and chemokine (C-X-C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1-F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling. Conclusion: In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high-risk individuals.
MIT Department
Ludwig Center for Molecular Oncology (Massachusetts Institute of Technology)
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Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International Licens
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DOI of Published Version
https://doi.org/10.1002/HEP4.1789
