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Gemigliptin Alleviates Succinate-Induced Hepatic Stellate Cell Activation by Ameliorating Mitochondrial Dysfunction.
- Source :
-
Endocrinology & Metabolism . Dec2022, Vol. 37 Issue 6, p918-928. 11p. - Publication Year :
- 2022
-
Abstract
- Background: Dipeptidyl peptidase-4 inhibitors (DPP-4Is) are used clinically as oral antidiabetic agents. Although DPP-4Is are known to ameliorate liver fibrosis, the protective mechanism of DPP-4Is in liver fibrosis remains obscure. In this study, gemigliptin was used to investigate the potential of DPP-4Is to alleviate the progression of liver fibrosis. Methods: To clarify the effects and mechanisms of gemigliptin, we conducted various experiments in LX-2 cells (immortalized human hepatic stellate cells [HSCs], the principal effectors of hepatic fibrogenesis), which were activated by succinate and exhibited elevated expression of α-smooth muscle actin, collagen type 1, and pro-inflammatory cytokines and increased cell proliferation. In vivo, we examined the effects and mechanisms of gemigliptin on a high-fat, high-cholesterol--induced mouse model of nonalcoholic steatohepatitis (NASH). Results: Gemigliptin decreased the expression of fibrogenesis markers and reduced the abnormal proliferation of HSCs. In addition, gemigliptin reduced the succinate-induced production of mitochondrial reactive oxygen species (ROS), intracellular ROS, and mitochondrial fission in HSCs. Furthermore, in the mouse model of NASH-induced liver fibrosis, gemigliptin alleviated both liver fibrosis and mitochondrial dysfunction. Conclusion: Gemigliptin protected against HSC activation and liver fibrosis by alleviating mitochondrial dysfunction and ROS production, indicating its potential as a strategy for preventing the development of liver disease. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LIVER cells
*HEPATIC fibrosis
*CD26 antigen
*MITOCHONDRIA
*REACTIVE oxygen species
Subjects
Details
- Language :
- English
- ISSN :
- 2093596X
- Volume :
- 37
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Endocrinology & Metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 162829605
- Full Text :
- https://doi.org/10.3803/EnM.2022.1530