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- W4381376722 abstract "Objective: Studies had found that homozygous mutations at p.R707W in the mitofusin-2 (MFN2) gene cause severe lipids metabolic abnormalities, and the mechanism has not been elucidated. In this study, we aim to explore the effect of the mutant protein on hepatocyte lipids deposition. Methods: Primary hepatocytes of wild-type (WT), heterozygous and homozygous mutation were isolated from 8 weeks old mice. Hepatocytes were treated with 600μmol/L free fat acid (FFA) of oleic acid/palmitic acid (2︰1) mixture for 12 hours to establish a NAFLD model in vitro. The lipid accumulation of hepatocytes was observed by Oil red O staining and the contents of triglyceride (TG). Results: Mutant mice carrying a novel p.R707W (CGA to TGG) mutation and silent mutation (p.D708=(GAT to GAC)) were identified (Fig. 1A). The results of Oil Red O staining and TG content measurement before FFA treating showed that more lipid was deposited in the homozygous hepatocyte than in WT cells (Fig. 1B, Fig. 1C) (*P<0.05), revealing that different genotypes of mice already have varied liver lipid contents at 8 weeks. After stimulation with FFA, TG content and lipidosis area in homozygous hepatocytes were significantly higher than those in WT (**P<0.01). And there was no significant difference between heterozygote and WT hepatocytes with or without FFA stimulation. Conclusion: Homozygous mutation at p.R707W in MFN2 aggravated lipid deposition in mouse. Disclosure Y.Yu: None. Y.Luo: None. X.Zhou: None. L.Ji: Other Relationship; Eli Lilly and Company, Novo Nordisk, Merck & Co., Inc., Bayer Inc., Sanofi-Aventis U.S., Roche Pharmaceuticals, MSD Life Science Foundation, AstraZeneca, Boehringer Ingelheim Inc., Abbott, Metronics. Funding China International Medical Foundation (2021-N-03)" @default.
- W4381376722 created "2023-06-21" @default.
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- W4381376722 date "2023-06-20" @default.
- W4381376722 modified "2023-10-12" @default.
- W4381376722 title "1596-P: Homozygous Mutations in MFN2 Aggravated Fat Deposition in Mouse Hepatocytes" @default.
- W4381376722 doi "https://doi.org/10.2337/db23-1596-p" @default.
- W4381376722 hasPublicationYear "2023" @default.
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