Role of autophagy in betaine-promoted hepatoprotection against non-alcoholic fatty liver disease in mice

IF 6.2 2区 农林科学 Q1 FOOD SCIENCE & TECHNOLOGY
Jinuk Seo , Doyoung Kwon , Sou Hyun Kim , Mi Ran Byun , Yun-Hee Lee , Young-Suk Jung
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引用次数: 0

Abstract

Betaine, a compound found in plants and sea foods, is known to be beneficial against non-alcoholic fatty liver disease (NAFLD), but its hepatoprotective and anti-steatogenic mechanisms have been not fully understood. In the present study, we investigated the mechanisms underlying betaine-mediated alleviation of NAFLD induced by a choline-deficient, L-amino acid-defined, high-fat diet (CDAHFD) in mice, with special focus on the contribution of betaine-stimulated autophagy to NAFLD prevention. Male ICR mice were fed a CDAHFD with or without betaine (0.2–1% in drinking water) for 1 week. Betaine ameliorated the CDAHFD-induced fatty liver by restoring sulfur amino acid (SAA)-related metabolites, such as S-adenosylmethionine and homocysteine, and the phosphorylation of AMPK and ACC. In addition, it reduced the CDAHFD-induced ER stress (BiP, ATF6, and CHOP) and apoptosis (Bax, cleaved caspase-3, and cleaved PARP); however, it induced autophagy (LC3II/I and p62) which was downregulated by CDAHFD. To determine the role of autophagy in the improvement of NAFLD, chloroquine (CQ), an autophagy inhibitor, was injected into the mice fed a CDAHFD and betaine (0.5 % in drinking water). CQ did not affect SAA metabolism but reduced the beneficial effects of betaine as shown by the increases of hepatic lipids, ER stress, and apoptosis. Notably, the betaine-induced improvements in lipid metabolism determined by protein levels of p-AMPK, p-ACC, PPARα, and ACS1, were reversed by CQ. Thus, the results of this study suggest that the activation of autophagy is an important upstream mechanism for the inhibition of steatosis, ER stress, and apoptosis by betaine in NAFLD.

Abstract Image

自噬在甜菜碱促进的小鼠非酒精性脂肪肝肝脏保护中的作用
已知甜菜碱是一种存在于植物和海洋食品中的化合物,对非酒精性脂肪肝(NAFLD)有益,但其保肝和抗致畸机制尚未完全清楚。在本研究中,我们研究了甜菜碱介导的缓解胆碱缺乏、L-氨基酸定义的高脂饮食(CDAHFD)诱导的小鼠非酒精性脂肪肝的机制,特别关注甜菜碱刺激自噬对预防非酒精性脂肪肝的贡献。雄性ICR小鼠在添加或不添加甜菜碱(在饮用水中添加0.2-1%)的CDAHFD条件下饲喂1周。甜菜碱通过恢复硫氨基酸(SAA)相关代谢物,如S-腺苷蛋氨酸和同型半胱氨酸,以及AMPK和ACC的磷酸化,改善了CDAHFD诱导的脂肪肝。此外,它还降低了CDAHFD诱导的ER应激(BiP、ATF6和CHOP)和细胞凋亡(Bax、裂解的caspase-3和裂解的PARP);然而,它诱导了自噬(LC3II/I和p62),而CDAHFD则下调了自噬。为了确定自噬在改善非酒精性脂肪肝中的作用,给喂食CDAHFD和甜菜碱(在饮用水中添加0.5%)的小鼠注射了自噬抑制剂氯喹(CQ)。CQ 不会影响 SAA 代谢,但会降低甜菜碱的有益作用,表现为肝脏脂质、ER 应激和细胞凋亡的增加。值得注意的是,根据 p-AMPK、p-ACC、PPARα 和 ACS1 蛋白水平测定的甜菜碱诱导的脂质代谢改善被 CQ 逆转。因此,本研究结果表明,激活自噬是甜菜碱抑制非酒精性脂肪肝患者脂肪变性、ER应激和细胞凋亡的重要上游机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Current Research in Food Science
Current Research in Food Science Agricultural and Biological Sciences-Food Science
CiteScore
7.40
自引率
3.20%
发文量
232
审稿时长
84 days
期刊介绍: Current Research in Food Science is an international peer-reviewed journal dedicated to advancing the breadth of knowledge in the field of food science. It serves as a platform for publishing original research articles and short communications that encompass a wide array of topics, including food chemistry, physics, microbiology, nutrition, nutraceuticals, process and package engineering, materials science, food sustainability, and food security. By covering these diverse areas, the journal aims to provide a comprehensive source of the latest scientific findings and technological advancements that are shaping the future of the food industry. The journal's scope is designed to address the multidisciplinary nature of food science, reflecting its commitment to promoting innovation and ensuring the safety and quality of the food supply.
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