Multiomic atlas of steatosis to NASH progression in mice

The global prevalence of nonalcoholic fatty liver disease (NAFLD) is estimated at 25% and will continue to rise
.
NAFLD encompasses a range of liver diseases, from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH).

NAFL is generally considered a benign condition, and NASH is prone to progression to severe end-stage liver disease
.
However, the molecular mechanism by which steatosis progresses to NASH remains poorly
understood.

Researchers from Shanghai Sixth People's Hospital and Anhui Medical University First Affiliated Hospital of Shanghai Jiao Tong University School of Medicine and other collaborators jointly presented comprehensive multiomic analyses to identify genes, noncoding RNAs, proteins, and plasma metabolites
associated with steeatosis to NASH progression, using two diet-induced NAFL and NASH mouse models.
The study, titled "Steatosis to the Multiomics Landscape of NASH Progression," was published in Metabolism of Life on December 2, 2022
.

In this study, fed using a two-stage HFHC diet, the authors performed a large-scale meta-analysis
of liver tissue from NAFL and NASH mice and their age-matched normal control groups.
Overall, multiomics studies captured 176 mRNAs, 1131 lncRNAs, 48 miRNAs, 295 proteins, and 53 plasma metabolites
in NAFL mice compared to age-matched normal mice.
At the same time, 1745 mRNAs, 5161 lncRNAs, 146 miRNAs, 674 proteins, and 82 plasma metabolites were altered
in NASH mice compared to age-matched normal mice.
By comparing these alterations in the two mouse models, a total of 1630 mRNAs, 4547 lncRNAs, 110 miRNAs, 500 proteins, and 46 plasma metabolites were specifically altered
in NASH mice compared to NAFL mice.
Therefore, this study provides a valuable resource
for exploring the molecular mechanism of steatosis-NASH progression.

Furthermore, through transcriptomic analysis, the authors found that growth differentiation factor (GDF3) was specifically upregulated
in the liver and plasma of NASH mice.
Compared with NAFL patients or healthy individuals, plasma GDF3 concentrations are significantly elevated
in patients with NASH.
Plasma GDF3 levels are strongly correlated with NAFLD activity scores (NAS) and individual histological features including steatosis, balloonization, and lobular inflammation (Figure 1).

The authors further evaluated the diagnostic potential of circulating GDF3, and the results showed that it can be used as a non-invasive diagnostic biomarker in patients with NASH with high accuracy (AUROC = 0.
90).

In conclusion, this study explores the molecular characteristics of steatosis-NASH progression in mice through large-scale systems biology methods, which may provide valuable resources
for exploring the molecular mechanism of NASH progression.
In addition, GDF3 may be considered a potential non-invasive diagnostic for patients with NASH, although further research is needed to explore its role in
NASH progression.