Salicornia Extract Ameliorates Salt‐Induced Aggravation of Nonalcoholic Fatty Liver Disease in Obese Mice Fed a High‐Fat Diet

High‐fat and high‐salt intakes are among the major risks of chronic diseases including obesity, nonalcoholic fatty liver disease (NAFLD), and nonalcoholic steatohepatitis (NASH). Salicornia is a halophytic plant known to exert antioxidant, antidiabetic, and hypolipidemic effects, and Salicornia‐extracted salt (SS) has been used as a salt substitute. In this study, the effects of SS and purified salt (PS) on the aggravation of NAFLD/NASH were compared. C57BL/6J male mice (8‐wk‐old) were fed a high‐fat diet (HFD) for 6 mo and divided into 3 dietary groups, which were additionally fed HFD, HFD + SS, and HFD + PS for 13 wk. PS induced aggravation of NAFLD/NASH in HFD‐fed mice. Although the actual salt intake was same between the PS and SS groups as 1% of the diet (extrapolated from the World Health Organization [WHO] guideline), SS induced less liver injury and hepatic steatosis compared to PS. The hepatic mRNA expressions of inflammatory cytokines and fibrosis marker were significantly lower in the SS group than the PS group. Oxidative stress is one of the major causes of inflammation in NAFLD/NASH. Results of the component analysis showed that the major polyphenols that exhibited antioxidant activity in the Salicornia water extract were ferulic acid, caffeic acid, and isorhamnetin. These results suggest that even the level of salt intake recommended by WHO can accelerate the progression of liver disease in obese individuals consuming HFD. It is proposed that SS can be a salt substitute for obese individuals who consume HFD.     

表没食子儿茶素没食子酸酯对小鼠非酒精性脂肪肝的干预作用

本文研究了表没食子儿茶素没食子酸酯(EGCG)对小鼠非酒精性脂肪性肝病(NAFLD)的干预作用。应用高脂饲料喂养Apo E-/-小鼠建立NAFLD小鼠模型,研究EGCG对NAFLD小鼠血液和肝组织中糖脂代谢、脂肪酸氧化、氧化应激水平、肝组织结构以及AMPK/SIRT1/SREBP-1c/PPARγ信号通路相关基因表达的影响。结果表明EGCG治疗后肝组织病理学变化明显改善,小鼠体质量、肝质量、肝质量指数较模型组显著降低至110.98%、115.01%,115.64%、136.48%和104.20%、118.70%(p<0.01);血液和肝组织中糖脂代谢、脂肪酸氧化、氧化应激水平改善幅度在11.85%~86.06%之间,与模型组比较具有显著性差异(p<0.05或p<0.01);升高肝组织中AMPKα、SIRT1 mRNA及p-AMPKα、SIRT1蛋白表达幅度在13.21%~75.82%之间,降低肝组织FASN、ACC-1、SREBP-1c、SCD-1、PPARγm RNA和FASN、p-ACC-1、p-SREBP-1c、SCD-1、PPARγ蛋白表达幅度在19.59%~92.07%之间,改善p-AMPKα/AMPKα、p-ACC-1/ACC-1和p-SREBP-1c/SREBP-1c比率在39.20%~93.07%之间,与模型组比较具有显著性差异(p<0.05或p<0.01)。本研究表明EGCG可通过调控AMPK/SIRT1/SREBP-1c/PPARγ信号通路相关基因的表达来改善NAFLD小鼠糖脂代谢、脂肪酸氧化和氧化应激状态。     

The Gut Microbiota and Its Metabolites,Novel Targets for Treating and Preventing Non‐Alcoholic Fatty Liver Disease

Non‐alcoholic fatty liver disease (NAFLD) is one of the most prevalent metabolic disorders worldwide, along with obesity and type 2 diabetes. NAFLD involves a series of liver abnormalities from simple hepatic steatosis to non‐alcoholic steatohepatitis, which can ultimately lead to liver cirrhosis and cancer. The gut–liver axis plays an important role in the development of NAFLD, which depends mainly on regulation of the gut microbiota and its bacterial products. These intestinal bacterial species and their metabolites, including bile acids, tryptophan catabolites, and branched‐chain amino acids, regulate adipose tissue and intestinal homeostasis and contribute to the pathogenesis of NAFLD/non‐alcoholic steatohepatitis. In this review, the current evidence regarding the key role of the gut microbiota and its metabolites in the pathogenesis and development of NAFLD is highlighted, and the advances in the progression and applied prospects of gut microbiota‐targeted dietary and exercise therapies is also discussed.     

刺梨多糖对非酒精性脂肪肝小鼠回肠黏膜屏障功能的影响

为研究刺梨多糖（Rosa roxburghii Tratt polysaccharides,RTFP）对非酒精性脂肪肝（non-alcoholic fatty liver disease,NAFLD）诱导的小鼠回肠肠道黏膜屏障功能障碍和肠道炎症的改善作用,以及刺梨多糖对肠道菌群的影响,本研究采用高脂肪饮食（high fat diet,HFD）喂养小鼠,构建NAFLD小鼠模型,然后灌胃RTFP,干预7周。结果表明,RTFP可显著降低NAFLD诱导的小鼠回肠炎症因子和氧化应激水平,改善脂质代谢紊乱状况。微观组织病理学观察发现,RTFP可以使小鼠回肠结构形态趋向于正常水平,减少隐窝病变,保护肠道屏障。通过16S rRNA高通量测序评估各处理组小鼠粪便微生物群的变化,发现RTFP可调节NAFLD小鼠肠道菌群的多样性和组成,厚壁菌门（Firmicutes）与拟杆菌门（Bacteroidetes）比值明显降低,提高了有益菌群的相对丰度,降低了病原菌群的相对丰度。RTFP可以作为一种益生元调节肠道菌群,改善NAFLD模型小鼠的肠道微生态,减轻肠道屏障功能障碍,维持肠道正常功能。     

富硒绿茶对大鼠非酒精性脂肪肝Ca2+-ATPase活性和表达的影响

目的：研究恩施富硒绿茶对大鼠非酒精性脂肪肝病（nonalcoholic fatty liver disease,NAFLD）中肝脏肌浆网/内质网Ca2+-ATPase（sarco（endo）plasmic reticulum Ca2+-ATPase,SERCA）活性及其表达的影响,探讨富硒绿茶防治NAFLD的可能作用机制。方法：将32 只Wistar大鼠分成4 组,分别饲喂标准饲料＋常规饮水（NC组）、高脂饲料＋常规饮水（HC组）、高脂饲料＋普通绿茶（TC组）、高脂饲料＋富硒绿茶（SeC组）。9 周后处死,观察大鼠一般情况,测定肝细胞内Ca2+含量、肿瘤坏死因子-α（tumor necrosis factor-α,TNF-α）水平、肝脏组织ATPase活性;采用免疫组化染色和Western blotting检测肝脏内总SERCA蛋白表达,观察各指标变化情况。结果：HC组大鼠肝细胞内Ca2+含量明显增高,Na+-K+-ATPase、Ca2+-ATPase活性降低,SERCA蛋白表达降低;富硒绿茶干预后Ca2+含量降低,酶活性升高,表达增加,较普通绿茶效果明显。结论：富硒绿茶对高脂饮食诱导的大鼠非酒精性脂肪肝病具有干预作用,可能是通过降低肝细胞内Ca2+和TNF-α含量而改善肝脏能量代谢障碍,同时提高了SERCA活性,增强其蛋白表达而实现的。