| International Session（Symposium）3(JSGE・JSH・JSGS・JSGCS) |
| Fri. November 1st 9:30 - 11:30 Room 4: Portopia Hotel South Wing Portopia Hall |
| Imeglimin suppresses liver fibrosis development through improvement of mitochondrial function in non-diabetic MASH mice | |||
| Kosuke Kaji1, Norihisa Nishimura1, Hitoshi Yoshiji1 | |||
| 1Department of Gastroenterology, Nara Medical University | |||
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| Background and Aim: Imeglimin, a novel anti-diabetic agent, has a potential to inhibit gluconeogenesis in liver and improve glucose uptake in skeletal muscle, in addition to promote insulin secretion in pancreas in a glucose-dependent manner. Meanwhile, imeglimin is reported to improve mitochondrial function in hepatocytes. However, the effects on MASH have not been clarified. This study examined the effect of imeglimin by non-antidiabetic action. Methods: Imeglimin was orally administered (100, 200 mg/kg:twice/day) to mice fed a choline-deficient high-fat diet (CDAHFD), and MASH pathology was evaluated after 8 weeks. In addition, its effect on palmitic acid (PA)-stimulated HepG2 cells was investigated. Results: In CDAHFD-fed mice, blood glucose was not elevated, but rather decreased, while marked hepatic steatosis, inflammation, and fibrosis were observed. Imeglimin-treated mice showed a suppression of steatosis, lipid peroxidation, hepatocyte apoptosis, Kupffer cells-mediated inflammatory response, resulting in reduced hepatic fibrosis. Imeglimin also augmented mitochondrial biosynthesis. Adipogenesis, inflammatory cytokine production, and apoptosis were induced in HepG2 stimulated with PA, all of which were significantly suppressed by the addition of imeglimin. In mitochondrial function, PA-stimulated reduction of TMRM fluorescence level, Complex-I, III, IV, and V activity, and oxygen consumption rate were improved and the expression of PGC-1a, mtTFA was increased by imeglimin. Conclusion: Imeglimin may ameliorate fatty acid-induced mitochondrial dysfunction in hepatocytes, thereby inhibiting lipogenesis and apoptosis, and improving MASH pathology even under non-diabetic conditions. |
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Index Term 1: MASH Index Term 2: mitochondrial function |
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