Mild methylenetetrahydrofolate reductase deficiency accelerates liver triacylglycerol and uric acid accumulation in fructose-fed mice

文献类型： 外文期刊

第一作者： Sun, Danda

作者： Sun, Danda;Tang, Chaohua;Zhao, Qingyu;Qin, Yuchang;Zhang, Junmin;Sun, Danda;Tang, Chaohua;Zhao, Qingyu;Zhang, Junmin;Zhang, Xueming

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关键词： Methylenetetrahydrofolate; reductase; Fructose; Lipidomic; Liver; Steatosis

期刊名称：NUTRITION RESEARCH （ 影响因子：3.876； 五年影响因子：3.934 ）

ISSN： 0271-5317

年卷期： 2022 年 108 卷

页码：

收录情况： SCI

摘要： A genetic predisposition to hepatic steatosis may be associated with dietary patterns. We hy-pothesized that a common variant in human methylenetetrahydrofolate reductase (MTHFR 677C -> T) was previously associated with an increased risk of nonalcoholic fatty liver dis-ease (NAFLD). In this study, we investigated the relationship between the human MTHFR polymorphism and NAFLD using fructose-fed male C57BL/6 Mthfr+/+ and Mthfr+/- mice, a model for the human gene variant. Mice were fed an 8% fructose solution for 12 weeks. Mthfr+/- mice had significantly increased abdominal fat mass and hepatic triglyceride (TG) but displayed a similar liver mass when compared with Mthfr+/ + mice. Liver morphology showed that mild MTHFR deficiency induced liver lipid droplet deposition and inflamma-tory cell infiltration, suggesting accelerated lipid accumulation in the liver. Moreover, mild MTHFR deficiency increased hepatic xanthine oxidase activity and uric acid accumulation. Using untargeted lipidomics, we identified 116 differentially expressed lipids species in the liver of Mthfr+/- mice when compared with Mthfr+/+ animals. The most significant lipid increase was observed in 47 TGs, followed by 33 phosphatidylcholines in Mthfr+/- mice liver. When compared with Mthfr+/+ liver, 9 TGs were dramatically decreased in Mthfr+/- liver. These changes were associated with upregulated gene expressions related to triglyc-eride synthesis and storage. Thus, Mthfr+/- mice developed NAFLD disease. These findings

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