关键词: NAFLD carnosine insulin resistance oxidative stress quantitative proteomics

Mesh : Humans Rats Animals Non-alcoholic Fatty Liver Disease / etiology chemically induced Carnosine / pharmacology therapeutic use Diet, Western / adverse effects Proteomics / methods Liver / metabolism Models, Animal Diet, High-Fat Lipid Metabolism Disease Models, Animal

来  源:   DOI:10.1002/jbt.23644

Abstract:
The nonalcoholic fatty liver disease (NAFLD), which is closely related to westernized dietary (WD) patterns, displays a rising epidemiological and economic burden. Since there is no pharmacological therapy approved for this disease, mechanistic studies are warranted. In this work, we investigated the action of carnosine (CAR), a natural dipeptide with several protection roles against oxidative stress in the liver of NAFLD rats. NAFLD was induced by WD-rich sugars and fat, verifying the histological evidence of steatosis. As intraperitoneal administration of CAR reversed liver steatosis, the protein profiles of NAFLD liver and CAR NAFLD liver were evaluated by label-free proteomics approach. A total of 2531 proteins were identified and the 230 and 276 were significantly up- and downregulated, respectively, by CAR treatment of NAFLD rats and involved in fundamental pathways such as oxidative stress and lipid metabolism. Perilipin 2 and apolipoprotein E, components of the plasma membrane of vesicle, resulted in highly downregulated in the CAR-treated NAFLD liver. The advanced bioanalytical approach demonstrated the efficacy of CAR in overcoming the main symptoms of NAFLD, ameliorating the steatosis in the liver.
摘要:
非酒精性脂肪性肝病(NAFLD),这与西方化饮食(WD)模式密切相关,显示出不断上升的流行病和经济负担。由于没有批准治疗这种疾病的药物治疗,机械研究是有必要的。在这项工作中,我们调查了肌肽(CAR)的作用,一种天然的二肽,在NAFLD大鼠肝脏中具有多种针对氧化应激的保护作用。NAFLD是由富含WD的糖和脂肪诱导的,验证脂肪变性的组织学证据。作为腹腔内施用CAR逆转肝脏脂肪变性,通过无标记蛋白质组学方法评估NAFLD肝脏和CARNAFLD肝脏的蛋白质谱.共鉴定出2531种蛋白质,其中230种和276种显著上调和下调,分别,通过CAR治疗NAFLD大鼠,并参与氧化应激和脂质代谢等基本途径。Perilipin2和载脂蛋白E,囊泡质膜的成分,导致CAR治疗的NAFLD肝脏高度下调。先进的生物分析方法证明了CAR在克服NAFLD主要症状方面的功效,改善肝脏脂肪变性。
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