- Book学术

发布求助

文献互助智能选刊最新文献

IF 3.7 3区医学 Q2 NUTRITION & DIETETICS

Journal of Nutrition Pub Date : 2025-03-13 DOI:10.1016/j.tjnut.2025.03.012

Chuan Chen, Xuebo Liu, Jiawei Wang, Xiaobo Wen, Huihong Zhao, Guanghui Chen, Kun Wu

{"title":"Zinc-Mediated Deacetylation of FXR Activates the ATGL Pathway to Reduce Hepatic Lipid Accumulation and Enhance Lipolysis in Yellow Catfish.","authors":"Chuan Chen, Xuebo Liu, Jiawei Wang, Xiaobo Wen, Huihong Zhao, Guanghui Chen, Kun Wu","doi":"10.1016/j.tjnut.2025.03.012","DOIUrl":null,"url":null,"abstract":"Background: High-fat diets (HFD) can lead to excessive accumulation of lipids in the liver, leading to liver injury. Dietary zinc (Zn) has been shown to reduce high-fat diets-induced lipid accumulation and improve lipid profiles in mammals, yet it remains unclear whether waterborne Zn maintains its lipid-lowering effects in osteichthyes.Objective: This study aimed to elucidate the regulatory role of Zn in high fat diet-induced hepatic lipid accumulation in yellow catfish (Pelteobagrus fulvidraco) and its potential mechanisms.Methods: Yellow catfish were fed a control diet (11.21% lipid level), high-fat diets (HFD) (16.10% lipid level), or an HFD combined with waterborne Zn exposure (0.2 mg/L) for 8 weeks. Various biochemical, genetic, histological, and molecular techniques were conducted to evaluate hepatic lipid deposition and lipid metabolism, and determine protein interactions between silent information regulator 1 (SIRT1) and farnesoid X receptor (FXR), as well as protein-gene interactions between FXR and adipose triglyceride lipase (ATGL).Results: HFD feeding significantly increased liver fat content and induced hepatic damage in yellow catfish, but concurrent exposure to waterborne Zn alleviated these detrimental effects. Zn treatment increased mRNA and protein levels of SIRT1 (97.19% ± 11.67% and 83.25% ± 28.60%, values are expressed as mean ± standard error of means, same below.) and FXR (163.90% ± 24.60%, 24.90% ± 11.12%) in yellow catfish liver (P < 0.05). Zn-activated FXR directly interacted with the promoter of ATGL, stimulating the expression of atgl (54.40% ± 16.33%, P < 0.05) and facilitating the hydrolysis of triglycerides and lipid droplets. Furthermore, Zn reduced the acetylation level of FXR by SIRT1 deacetylation of FXR protein K167.Conclusions: The findings revealed that Zn protect against HFD-induced liver injury in yellow catfish by promoting the deacetylation of FXR protein K167 by SIRT1 and activating FXR, thereby promoting the transcriptional activation of ATGL to increase lipolysis.","PeriodicalId":16620,"journal":{"name":"Journal of Nutrition","volume":" ","pages":""},"PeriodicalIF":3.7000,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nutrition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tjnut.2025.03.012","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}

引用次数: 0

摘要

背景：高脂饮食（HFD）会导致肝脏中脂质过度积累，从而导致肝损伤。膳食锌（Zn）已被证明可减少高脂饮食诱导的脂质积累并改善哺乳动物的脂质状况，但目前仍不清楚水载锌是否能维持其在骨鱼中的降脂作用：本研究旨在阐明锌在黄颡鱼（Pelteobagrus fulvidraco）高脂饮食诱导的肝脏脂质积累中的调节作用及其潜在机制：给黄颡鱼喂食对照日粮（脂质含量为 11.21%）、高脂日粮（脂质含量为 16.10%）或高脂日粮结合水载锌暴露（0.2 毫克/升）8 周。研究人员采用了各种生化、遗传、组织学和分子技术来评估肝脏脂质沉积和脂质代谢，并确定了沉默信息调节因子1（SIRT1）与法呢类X受体（FXR）之间的蛋白质相互作用，以及FXR与脂肪甘油三酯脂肪酶（ATGL）之间的蛋白质基因相互作用：高密度脂蛋白胆固醇（HFD）喂养会明显增加黄颡鱼肝脏脂肪含量并诱发肝损伤，但同时接触水载锌可减轻这些不利影响。锌处理提高了黄颡鱼肝脏中 SIRT1（97.19% ± 11.67% 和 83.25% ± 28.60%，以均数 ± 标准误差表示，下同）和 FXR（163.90% ± 24.60%，24.90% ± 11.12%）的 mRNA 和蛋白质水平（P < 0.05）。Zn 激活的 FXR 直接与 ATGL 的启动子相互作用，刺激 ATGL 的表达（54.40% ± 16.33%，P < 0.05），促进甘油三酯和脂滴的水解。此外，Zn 通过 SIRT1 对 FXR 蛋白 K167 的去乙酰化作用降低了 FXR 的乙酰化水平：研究结果表明，锌通过促进 SIRT1 对 FXR 蛋白 K167 的去乙酰化和激活 FXR，从而促进 ATGL 的转录活化以增加脂肪分解，对 HFD 诱导的黄颡鱼肝损伤具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

查看原文本刊更多论文

Zinc-Mediated Deacetylation of FXR Activates the ATGL Pathway to Reduce Hepatic Lipid Accumulation and Enhance Lipolysis in Yellow Catfish.

Background: High-fat diets (HFD) can lead to excessive accumulation of lipids in the liver, leading to liver injury. Dietary zinc (Zn) has been shown to reduce high-fat diets-induced lipid accumulation and improve lipid profiles in mammals, yet it remains unclear whether waterborne Zn maintains its lipid-lowering effects in osteichthyes.

Objective: This study aimed to elucidate the regulatory role of Zn in high fat diet-induced hepatic lipid accumulation in yellow catfish (Pelteobagrus fulvidraco) and its potential mechanisms.

Methods: Yellow catfish were fed a control diet (11.21% lipid level), high-fat diets (HFD) (16.10% lipid level), or an HFD combined with waterborne Zn exposure (0.2 mg/L) for 8 weeks. Various biochemical, genetic, histological, and molecular techniques were conducted to evaluate hepatic lipid deposition and lipid metabolism, and determine protein interactions between silent information regulator 1 (SIRT1) and farnesoid X receptor (FXR), as well as protein-gene interactions between FXR and adipose triglyceride lipase (ATGL).

Results: HFD feeding significantly increased liver fat content and induced hepatic damage in yellow catfish, but concurrent exposure to waterborne Zn alleviated these detrimental effects. Zn treatment increased mRNA and protein levels of SIRT1 (97.19% ± 11.67% and 83.25% ± 28.60%, values are expressed as mean ± standard error of means, same below.) and FXR (163.90% ± 24.60%, 24.90% ± 11.12%) in yellow catfish liver (P < 0.05). Zn-activated FXR directly interacted with the promoter of ATGL, stimulating the expression of atgl (54.40% ± 16.33%, P < 0.05) and facilitating the hydrolysis of triglycerides and lipid droplets. Furthermore, Zn reduced the acetylation level of FXR by SIRT1 deacetylation of FXR protein K167.

Conclusions: The findings revealed that Zn protect against HFD-induced liver injury in yellow catfish by promoting the deacetylation of FXR protein K167 by SIRT1 and activating FXR, thereby promoting the transcriptional activation of ATGL to increase lipolysis.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Journal of Nutrition 医学-营养学

CiteScore

7.60

自引率

4.80%

发文量

260

审稿时长

39 days

期刊介绍： The Journal of Nutrition (JN/J Nutr) publishes peer-reviewed original research papers covering all aspects of experimental nutrition in humans and other animal species; special articles such as reviews and biographies of prominent nutrition scientists; and issues, opinions, and commentaries on controversial issues in nutrition. Supplements are frequently published to provide extended discussion of topics of special interest.