Institute of Drug Discovery Technology, Ningbo University, Ningbo 315211, China.
Qian Xuesen Collaborative Research Center of Astrochemistry and Space Life Sciences, Ningbo University, Ningbo 315211, China.
Nutrients. 2023 Sep 14;15(18):3988. doi: 10.3390/nu15183988.
Non-alcoholic fatty liver disease (NAFLD) manifests as a persistent liver ailment marked by the excessive buildup of lipids within the hepatic organ accompanied by inflammatory responses and oxidative stress. Alanyl-glutamine (AG), a dipeptide comprising alanine and glutamine, is commonly employed as a nutritional supplement in clinical settings. This research aims to evaluate the impact of AG on NAFLD triggered by a high-fat diet (HFD), while concurrently delving into the potential mechanisms underlying its effects. The results presented herein demonstrate a notable reduction in the elevated body weight, liver mass, and liver index induced by a HFD upon AG administration. These alterations coincide with the amelioration of liver injury and the attenuation of hepatic histological advancement. Furthermore, AG treatment manifests a discernible diminution in oil-red-O-stained regions and triglyceride (TG) levels within the liver. Noteworthy alterations encompass lowered plasma total cholesterol (TC) and low-density lipoprotein cholesterol (LDLC) concentrations, coupled with elevated high-density lipoprotein cholesterol (HDLC) concentrations. The mitigation of hepatic lipid accumulation resultant from AG administration is aligned with the downregulation of ACC1, SCD1, PPAR-γ, and CD36 expression, in conjunction with the upregulation of FXR and SHP expression. Concomitantly, AG administration leads to a reduction in the accumulation of F4/80-positive macrophages within the liver, likely attributable to the downregulated expression of MCP-1. Furthermore, AG treatment yields a decline in hepatic MDA levels and a concurrent increase in the activities of SOD and GPX. A pivotal observation underscores the effect of AG in rectifying the imbalance of gut microbiota in HFD-fed mice. Consequently, this study sheds light on the protective attributes of AG against HFD-induced NAFLD through the modulation of gut microbiota composition.
非酒精性脂肪性肝病（NAFLD）表现为一种持续的肝脏疾病，其特征是肝组织内脂质过度积累，伴有炎症反应和氧化应激。丙氨酰-谷氨酰胺（AG）是一种由丙氨酸和谷氨酰胺组成的二肽，在临床中常被用作营养补充剂。本研究旨在评估 AG 对高脂肪饮食（HFD）诱导的 NAFLD 的影响，同时探讨其作用的潜在机制。本文研究结果表明，AG 可显著降低 HFD 引起的体重、肝脏质量和肝脏指数升高。这些变化与肝损伤的改善和肝组织学进展的减弱相一致。此外，AG 治疗可明显减少肝脏中油红-O 染色区域和甘油三酯（TG）水平。值得注意的变化包括血浆总胆固醇（TC）和低密度脂蛋白胆固醇（LDLC）浓度降低，而高密度脂蛋白胆固醇（HDLC）浓度升高。AG 治疗减轻肝脏脂质积累的作用与 ACC1、SCD1、PPAR-γ 和 CD36 表达下调以及 FXR 和 SHP 表达上调相一致。同时，AG 给药可减少肝脏内 F4/80 阳性巨噬细胞的积累，这可能归因于 MCP-1 表达下调。此外，AG 治疗可降低肝脏 MDA 水平，同时增加 SOD 和 GPX 的活性。一个重要的观察结果强调了 AG 纠正 HFD 喂养小鼠肠道微生物群失衡的作用。因此，本研究通过调节肠道微生物群组成，揭示了 AG 对 HFD 诱导的 NAFLD 的保护作用。
