National Engineering Laboratory/Key Laboratory of Henan Province, College of Food Science and Engineering, Henan University of Technology, Zhengzhou 450001, China.
Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
Food Res Int. 2022 Aug;158:111507. doi: 10.1016/j.foodres.2022.111507. Epub 2022 Jun 15.
Methionine, an essential sulfur-containing amino acid, is associated with hepatic lipid accumulation; however, the underlying mechanism is unknown. This study aimed to investigate the effects of different dietary methionine levels on hepatic lipid accumulation in mice and clarify the possible mechanisms involved. The Institute of Cancer Research (ICR) mice were fed a normal diet (ND, 0.86% methionine), high-methionine diet (HMD, 2.58% methionine), or methionine-restricted diet (MRD, 0.17% methionine) for 11 consecutive weeks. Our results showed that HMD increased the liver weight and liver index, plasma and hepatic lipid profiles, and hepatic fatty infiltration area and perirenal fat volume. In addition, HMD promoted lipid synthesis, inhibited lipid catabolism and glycolysis metabolism, reduced the activities of mitochondrial respiratory chain enzyme complexes (Ⅰ and Ⅴ) and adenosine triphosphate (ATP) production, and elevated oxidative stress and inflammation in the liver. Moreover, HMD inhibited homocysteine metabolism and significantly decreased the expression and activity of cystathionine γ-lyase (CSE) and 3-mercaptopyruvate sulfurtransferase (3-MST), thereby reducing endogenous HS production in the liver. Interestingly, MRD reversed these adverse effects, and promoted endogenous HS production. In conclusion, inhibition of hepatic HS production may be the mechanism behind an increased risk of nonalcoholic fatty liver disease (NAFLD) associated with high dietary methionine intake. Therefore, it is necessary to reduce methionine intake in the daily diet to prevent NAFLD and maintain good physical health.
蛋氨酸是一种必需的含硫氨基酸，与肝脏脂质积累有关；然而，其潜在机制尚不清楚。本研究旨在探讨不同膳食蛋氨酸水平对小鼠肝脏脂质积累的影响，并阐明可能涉及的机制。研究人员用正常蛋氨酸饮食（ND，0.86%蛋氨酸）、高蛋氨酸饮食（HMD，2.58%蛋氨酸）或蛋氨酸限制饮食（MRD，0.17%蛋氨酸）连续喂养 ICR 小鼠 11 周。结果显示，HMD 增加了肝脏重量和肝脏指数、血浆和肝脏脂质谱以及肝脂肪浸润面积和肾周脂肪体积。此外，HMD 促进了脂质合成，抑制了脂质分解和糖酵解代谢，降低了线粒体呼吸链酶复合物（Ⅰ和Ⅴ）和三磷酸腺苷（ATP）的活性，增加了肝脏的氧化应激和炎症。此外，HMD 抑制了同型半胱氨酸代谢，显著降低了胱硫醚γ-裂解酶（CSE）和 3-巯基丙酮酸硫转移酶（3-MST）的表达和活性，从而减少了肝脏内源性 HS 的产生。有趣的是，MRD 逆转了这些不利影响，并促进了内源性 HS 的产生。总之，抑制肝脏 HS 的产生可能是高膳食蛋氨酸摄入增加非酒精性脂肪性肝病（NAFLD）风险的机制。因此，有必要减少日常饮食中的蛋氨酸摄入量，以预防 NAFLD 和保持良好的身体健康。
