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Gene & Protein in Disease Hydrogen sulfide ameliorates NAFLD

and a decrease in mTOR phosphorylation in mouse Furthermore, the exploration and validation of innovative
hepatocytes, as observed through Western blotting analysis. therapeutic agents hold significant importance.
Specifically, 100 μM NaHS led to the most significant increase In this study, our findings convincingly demonstrate
in AMPK phosphorylation, whereas 50 μM NaHS caused that NaHS, a hydrogen sulfide donor, exerts a profound
the most significant decrease in mTOR phosphorylation therapeutic effect on NAFLD in mice, effectively
levels (Figure 6A-C, Figure R1). Furthermore, we ameliorating the associated symptoms in both in vitro
investigated these phosphorylation changes in animal and in vivo studies. Based on transcriptome data analysis
models. In NaHS-treated HFD mice, the phosphorylation and Western blotting experiments, our findings present
levels of AMPK and mTOR mirrored the results observed preliminary evidence highlighting the significant role of
in cell culture. Specifically, NaHS treatment led to decreased cellular autophagy activation in mitigating the symptoms
phosphorylation of AMPK and increased phosphorylation
of mTOR in comparison to the control group, suggesting of NAFLD in mice.
that the AMPK mTOR pathway is inhibited in the liver tissue Acknowledgments
of HFD mice. Moreover, the expression of the autophagy
marker protein LC3BII was significantly elevated following None.
both starvation (which stimulates cellular autophagy) and
prolonged NaHS incubation (Figures 6D and E, Figure R2). Funding
Similar changes in LC3BII expression were observed in This research was funded by The Key R&D and Promotion
HFD mice treated with NaHS. Projects of Henan Province (232102311139); China

In addition, we assessed two autophagy-associated Postdoctoral Science Foundation (2021m690095); National
marker proteins, adipose differentiation-related protein Innovation and Entrepreneurship Training Program for
(ADRP) (lipid droplet protein) and p62, in the liver tissues College Students (202310475169); and Henan University
of HFD mice following NaHS treatment. Compared to the Research Laboratory Open Project for Undergraduate
HFD group, NaHS-treated mice exhibited decreased levels Students (20233001246 and 20233306208).
of both p62 and ADRP in their liver tissues. These findings Conflict of interest
suggest that NaHS treatment reactivates the AMPK-mTOR
pathway, leading to increased autophagy and decreased The authors declare no conflict of interest.
lipid droplet accumulation. These results are consistent
with the staining of mouse liver tissue sections and liver Author contributions
biochemical assays (Figure R3). Conceptualization: Na Chen, Tieshan Teng
4. Conclusion Investigation: Yuhan Wang
Methodology: Hanyue Zhuang, Jingjing Li
NAFLD has emerged as a significant threat to human Writing – original draft: Hanyue Zhuang, Jiangzhe Si
health, exerting a substantial burden on both individuals Writing – review & drafting: Zewei Yang, Waner Wang,
and society. This mounting concern is primarily Zimo Ge
attributed to the disease’s potential to cause substantial
occupational limitations and the high costs associated Ethics approval and consent to participate
with its treatment. Despite the expansive market for The study received approval (Approval ID: HUSOM2024-
therapeutic drugs aimed at addressing NAFLD, research 088) from the Institutional Animal Care and Use
and development in this field remain fiercely competitive. Committee (IACUC) at XXX.
Although numerous drugs are currently undergoing
clinical trials, no individual targeted drug has yet Consent for publication
obtained regulatory approval for marketing. At present,
the primary treatment options for NAFLD involve a Not applicable.
diverse range of lifestyle interventions recommended Availability of data
based on mechanistic research. In addition, there is
a growing trend of repurposing existing drugs with Data used in this work are available from the corresponding
established efficacy in enhancing insulin sensitivity, author upon reasonable request.
reducing lipid levels, and providing antioxidant benefits.
Given the present scenario, it becomes crucial to delve References
into the mechanisms underlying the development and 1. Chen Y, Gao WK, Shu YY, Ye J. Mechanisms of ductular
regression of NAFLD through fundamental experiments. reaction in non-alcoholic steatohepatitis. World J

Volume 3 Issue 3 (2024) 9 doi: 10.36922/gpd.3409