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Beneficial effects of inorganic nitrate in non-alcoholic fatty liver disease
Archives of Biochemistry and Biophysics ( IF 3.9 ) Pub Date : 2021-09-11 , DOI: 10.1016/j.abb.2021.109032
Yang Liu 1 , Kevin D Croft 1 , Jose Caparros-Martin 2 , Fergal O'Gara 3 , Trevor A Mori 4 , Natalie C Ward 5
Affiliation  

Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic representation of the metabolic disorders. Inorganic nitrate/nitrite can be converted to nitric oxide, regulate glucose metabolism, lower lipid levels, and reduce inflammation, thus raising the hypothesis that inorganic nitrate/nitrite could be beneficial for improving NAFLD. This study assessed the therapeutic effects of chronic dietary nitrate on NAFLD in a mouse model. 60 ApoE−/- mice were fed a high-fat diet (HFD) for 12 weeks to allow for the development of atherosclerosis with associated NAFLD. The mice were then randomly assigned to different groups (20/group) for a further 12 weeks: (i) HFD + NaCl (1 mmol/kg/day), (ii) HFD + NaNO3 (1 mmol/kg/day), and (iii) HFD + NaNO3 (10 mmol/kg/day). A fourth group of ApoE−/- mice consumed a normal chow diet for the duration of the study. At the end of the treatment, caecum contents, serum, and liver were collected. Consumption of the HFD resulted in significantly greater lipid accumulation in the liver compared to mice on the normal chow diet. Mice whose HFD was supplemented with dietary nitrate for the second half of the study, showed an attenuation in hepatic lipid accumulation. This was also associated with an increase in hepatic AMPK activity compared to mice on the HFD. In addition, a significant difference in bile acid profile was detected between mice on the HFD and those receiving the high dose nitrate supplemented HFD. In conclusion, dietary nitrate attenuates the progression of liver steatosis in ApoE−/- mice fed a HFD.



中文翻译:

无机硝酸盐对非酒精性脂肪肝的有益作用

非酒精性脂肪性肝病 (NAFLD) 被认为是代谢紊乱的肝脏表现。无机硝酸盐/亚硝酸盐可以转化为一氧化氮,调节葡萄糖代谢,降低脂质水平,减少炎症,从而提出无机硝酸盐/亚硝酸盐可能有益于改善 NAFLD 的假设。本研究评估了慢性膳食硝酸盐对小鼠模型中 NAFLD 的治疗效果。60 只 ApoE -/-小鼠被喂食高脂肪饮食 (HFD) 12 周,以允许动脉粥样硬化与相关 NAFLD 的发展。然后将小鼠随机分配到不同的组(20/组)再持续 12 周:(i)HFD + NaCl(1 mmol/kg/天),(ii)HFD + NaNO 3(1 mmol/kg/天) , (iii) HFD + NaNO 3(10 毫摩尔/公斤/天)。第四组 ApoE -/-小鼠在研究期间消耗正常食物。在治疗结束时,收集盲肠内容物、血清和肝脏。与正常食物的小鼠相比,HFD 的消耗导致肝脏中的脂质积累显着增加。在研究的后半部分,HFD 补充膳食硝酸盐的小鼠表现出肝脏脂质积累的减弱。与使用 HFD 的小鼠相比,这也与肝脏 AMPK 活性的增加有关。此外,在使用 HFD 的小鼠和接受高剂量硝酸盐补充的 HFD 的小鼠之间检测到胆汁酸谱的显着差异。总之,膳食硝酸盐可减缓 ApoE 中肝脂肪变性的进展-/- 喂食HFD的小鼠。

更新日期:2021-09-13
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