Altered Hepatic Hydrogen Sulfide-Related Homeostasis in Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Changes Following Sleeve Gastrectomy
4 affiliations
- 1Department of General Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
- 2Tianjin Key Laboratory of Precise Vascular Reconstruction and Organ Function Repair, Tianjin 300052, China
- 3Tianjin General Surgery Institute, Tianjin 300052, China
- 4Department of Vascular Surgery, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, Tianjin 300121, China
Abstract
Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and metabolic dysfunction. Hydrogen sulfide (H2S) is involved in hepatic glucose and lipid metabolism and redox homeostasis, but alterations in hepatic H2S-related homeostasis in MASLD and their changes following sleeve gastrectomy (SG) remain incompletely understood. This study investigated hepatic H2S metabolism in MASLD and its changes following SG. Methods: Liver tissues from five patients with MASLD and five non-MASLD controls were analyzed for histology, H2S levels, and expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST) by qPCR, Western blotting, and immunohistochemistry. A high-fat diet-induced obese rat model was used to evaluate the metabolic, biochemical, histological, and hepatic H2S-related effects of SG. Results: Patients with MASLD showed marked hepatic steatosis, a reduced hepatic H2S-related sulfide pool and CSE expression, increased MPST expression, and unchanged CBS expression. Similar alterations were observed in obese rats. Compared with Sham rats, SG reduced body weight and food intake, improved glucose and lipid metabolism and liver function, and attenuated hepatic steatosis. These improvements were accompanied by an increased hepatic H2S-related sulfide pool and CSE expression and decreased MPST expression, whereas CBS remained stable. Conclusions: MASLD was associated with altered hepatic H2S-related homeostasis characterized by a reduced H2S-related sulfide pool, decreased CSE expression, increased MPST expression, and relatively stable CBS expression. In obese rats, metabolic improvement following SG was accompanied by corresponding changes in hepatic H2S-related homeostasis toward the pattern observed in controls. Whether these H2S-related changes contribute functionally to the metabolic benefits of SG remains to be determined.
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BibTeX
@article{han2026altered,
title = {{Altered Hepatic Hydrogen Sulfide-Related Homeostasis in Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Changes Following Sleeve Gastrectomy}},
author = {Yitong Han and Junhang Chen and Yi Xu and Longhao Sun and Xiangchen Dai},
journal = {Journal of Clinical Medicine},
year = {2026},
month = nov,
doi = {10.3390/jcm15218514},
url = {https://www.mdpi.com/2077-0383/15/21/8514},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Altered Hepatic Hydrogen Sulfide-Related Homeostasis in Metabolic Dysfunction-Associated Steatotic Liver Disease and Its Changes Following Sleeve Gastrectomy
AU - Yitong Han
AU - Junhang Chen
AU - Yi Xu
AU - Longhao Sun
AU - Xiangchen Dai
PY - 2026
DA - 2026/11/02
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218514
UR - https://www.mdpi.com/2077-0383/15/21/8514
AB - Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely associated with obesity and metabolic dysfunction. Hydrogen sulfide (H2S) is involved in hepatic glucose and lipid metabolism and redox homeostasis, but alterations in hepatic H2S-related homeostasis in MASLD and their changes following sleeve gastrectomy (SG) remain incompletely understood. This study investigated hepatic H2S metabolism in MASLD and its changes following SG. Methods: Liver tissues from five patients with MASLD and five non-MASLD controls were analyzed for histology, H2S levels, and expression of cystathionine β-synthase (CBS), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (MPST) by qPCR, Western blotting, and immunohistochemistry. A high-fat diet-induced obese rat model was used to evaluate the metabolic, biochemical, histological, and hepatic H2S-related effects of SG. Results: Patients with MASLD showed marked hepatic steatosis, a reduced hepatic H2S-related sulfide pool and CSE expression, increased MPST expression, and unchanged CBS expression. Similar alterations were observed in obese rats. Compared with Sham rats, SG reduced body weight and food intake, improved glucose and lipid metabolism and liver function, and attenuated hepatic steatosis. These improvements were accompanied by an increased hepatic H2S-related sulfide pool and CSE expression and decreased MPST expression, whereas CBS remained stable. Conclusions: MASLD was associated with altered hepatic H2S-related homeostasis characterized by a reduced H2S-related sulfide pool, decreased CSE expression, increased MPST expression, and relatively stable CBS expression. In obese rats, metabolic improvement following SG was accompanied by corresponding changes in hepatic H2S-related homeostasis toward the pattern observed in controls. Whether these H2S-related changes contribute functionally to the metabolic benefits of SG remains to be determined.
SN - 2077-0383
ER -