Red and processed meat consumption has been associated with oxidative stress, diabetes and non-alcoholic fatty liver disease (NAFLD). This study was aimed at exploring the effects of high-fat meat protein diets on potential metabolite biomarkers in Glrx1-/- mice, a well-documented mouse model to study NAFLD. Male Glrx1-/- mice were fed a control diet with 12% energy (kcal) from fat, a high-fat diet supplemented with casein (HFC) with 60% energy (kcal) from fat, and a high-fat diet supplemented with fish (HFF) or mutton proteins (HFM) for 12 weeks. The results of biochemical and histological analyses indicated that the intake of HFM increased hepatic total cholesterol, triglycerides, serum alanine transaminase and aspartate transaminase, and macro- and micro-vesicular lipid droplet accumulation, which were accompanied by altered gene expression associated with the lipid and cholesterol metabolism. HFF diet fed Glrx1-/- mice significantly ameliorated diet-induced NAFLD biomarkers compared to HFC and HFM diets. In addition, serum metabolome profiling identified metabolites specifically associated with lipid metabolism bile acid metabolism, sphingolipid and amino acid metabolism pathways. A HFM diet increased the abundance of LysoPC(15:0), LysoPC(16:0), LysoPC(20:1), LysoPE(18:2), LysoPE(22:0), LysoPE(20:6), O-arachidonoylglycidol, 12-ketodeoxycholic acid and sphinganine that are associated with NAFLD. The KEGG metabolic pathway of identified metabolites of high fat diets showed that the differential metabolites were associated with lipid metabolism, linoleic acid metabolism, amino acid metabolism, bile acid metabolism, sphingolipid metabolism, and glutathione metabolism pathways whereas HFF diet ameliorated NAFLD by modifying these pathways. These results provide potential metabolite biomarkers for NAFLD induced by HFM diet.

中文翻译：

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高脂肪饮食与肉类蛋白质结合会改变Glrx1-/-小鼠脂质代谢，抗氧化活性和血清代谢组学特征的生物标志物。

食用红色肉和加工肉与氧化应激，糖尿病和非酒精性脂肪性肝病（NAFLD）有关。这项研究旨在探讨高脂肉蛋白饮食对Glrx1-/-小鼠中潜在的代谢物生物标志物的影响，Glrx1-/-小鼠是研究NAFLD的有据可查的小鼠模型。给雄性Glrx1-/-小鼠喂食对照饮食，其脂肪能量为12％（kcal），补充高脂饮食的酪蛋白（HFC）为60％脂肪能量（kcal），补充高脂饮食为鱼（HFF）或羊肉蛋白（HFM），持续12周。生化和组织学分析结果表明，摄入HFM会增加肝脏总胆固醇，甘油三酸酯，血清丙氨酸转氨酶和天冬氨酸转氨酶，以及大和微囊泡脂质滴的积累，它们伴随着与脂质和胆固醇代谢相关的基因表达改变。与HFC和HFM饮食相比，HFF饮食喂养的Glrx1-/-小鼠显着改善了饮食诱导的NAFLD生物标志物。另外，血清代谢物谱分析鉴定出与脂质代谢，胆汁酸代谢，鞘脂和氨基酸代谢途径特别相关的代谢产物。HFM饮食会增加LysoPC（15：0），LysoPC（16：0），LysoPC（20：1），LysoPE（18：2），LysoPE（22：0），LysoPE（20：6），O的丰度与花生四烯酸相关的花生四烯酸-花生四烯酰基缩水甘油，12-酮脱氧胆酸和鞘氨醇。高脂饮食中确定的代谢物的KEGG代谢途径表明，差异代谢物与脂质代谢，亚油酸代谢，氨基酸代谢，胆汁酸代谢，鞘脂代谢和谷胱甘肽代谢途径，而HFF饮食通过修饰这些途径改善了NAFLD。这些结果为HFM饮食诱导的NAFLD提供了潜在的代谢物生物标志物。