柚皮苷调节NAFLD小鼠脂代谢紊乱机制研究*

doi:10.3969/j.issn.1672-5069.2024.06.005

实用肝脏病杂志 ›› 2024, Vol. 27 ›› Issue (6): 816-819.doi: 10.3969/j.issn.1672-5069.2024.06.005

柚皮苷调节NAFLD小鼠脂代谢紊乱机制研究^*

贾纪会, 张译之, 林静, 兰佳庆, 陈煜, 段钟平, 张晓慧

100069 北京市首都医科大学附属北京佑安医院肝病中心四科(贾纪会,林静,陈煜,段钟平,张晓慧);附属北京友谊医院肝病中心重症肝病科(张译之);山西大同大学护理学院(兰佳庆)

收稿日期:2024-03-18 出版日期:2024-11-10 发布日期:2024-11-07
通讯作者: 张晓慧,E-mail:xiaohui.zhang@ccmu.edu.cn
作者简介:贾纪会,女,26,硕士研究生。E-mail:15064945917@163.com
基金资助:
^*北京市自然科学基金资助项目(编号:7202070);北京市高层次公共卫生技术人才建设基金资助项目(编号:学科骨干-02-24);首都医科大学附属北京佑安医院人才库培养计划项目(编号:YARCKC2022004);佑安医院北京市重点实验室开放研究课题(编号:BJYAHKF2023003);北京市医院管理中心“登峰”计划专项基金资助项目(编号:DFL20221501)

Down-regulation of hepatic SREBP1 and PPAR-γ expression by naringin in mice with high-fat diet-induced NAFLD

Jia Jihui, Zhang Yizhi, Lin Jing, et al

Fourth Department of Liver Disease, You’an Hospital, Capital Medical University, Beijing 100069, China

Received:2024-03-18 Online:2024-11-10 Published:2024-11-07

摘要/Abstract

摘要： 目的探讨柚皮苷(nar)对高脂饮食(HFD)诱导的非酒精性脂肪性肝病(NAFLD)小鼠肝组织脂代谢紊乱的影响。方法将24只C57BL/6J小鼠随机分为对照组(n=8)、高脂饮食组(HFD组,n=8)和柚皮苷干预组(HFD/Nar干预组,n=8)。采用转录组测序寻找药物干预差异基因富集通路,采用qPCR和Western Blot法检测肝组织脂代谢相关基因及其蛋白表达。结果与对照组比,模型组小鼠体质量增加了57.8%(P<0.01),而经柚皮苷干预后,小鼠体质量较模型组降低了13.5%(P<0.01);模型组小鼠肝组织TG和TC水平分别为(3.5±0.4)mmol/g protein和(3.1±0.5)mmol/g protein,均显著高于对照组[分别为(1.0±0.3)mmol/g protein和(0.8±0.1)mmol/g protein,P<0.01],而HFD/Nar干预组肝组织TG和TC较模型组显著下降[分别为(2.1±0.4)mmol/g protein和(1.11±0.3)mmol/g protein,P<0.05];转录组测序KEGG富集分析显示柚皮苷对与脂代谢通路相关的9条通路有显著影响,表现为柚皮苷干预可显著下调肝组织固醇调节元件结合蛋白1(SREBP1)、过氧化物酶体增殖激活受体(PPAR-γ)、CD36和肝型脂肪酸结合蛋白1(FABP1)表达(P<0.05),而上调PPAR-α和重组肉毒碱棕榈酰转移酶1a (CPT-1A)表达(P<0.05)。结论柚皮苷可明显改善NAFLD小鼠肝内脂质沉积,可能影响了有关基因表达而减少了脂质摄取、合成,加快脂肪酸氧化有关。

关键词: 非酒精性脂肪性肝病, 柚皮苷, 肝组织固醇调节元件结合蛋白1, 过氧化物酶体增殖激活受体, 肝型脂肪酸结合蛋白1, 重组肉毒碱棕榈酰转移酶1a, 小鼠

Abstract: Objective The purpose of this experiment was to investigate effects of naringin (Nar) on lipid metabolism in mice with high-fat diet (HFD) induced non-alcoholic fatty liver diseases (NAFLD). Methods Twenty-four C57BL/6J mice were randomly divided into control, model and HFD/Nar-intervention groups, with eight mice in each group. The model of NAFLD was established by HFD intake, and the intervention was carried out by naringin gavage at dose of 100 mg.kg^-1 for four weeks. Drug intervention with differential gene enrichment pathways was determined by transcriptome sequencing. Hepatic lipid metabolism related genes and their protein expression were detected by qPCR and Western blot. Results Body mass of mice in model group increased by 57.8% (P<0.01) as compared with in the control, while in naringin-intervention group, it decreased by 13.5% (P<0.01); hepatic TG and TC levels in the model were (3.5±0.4)mmol/g protein and (3.1±0.5)mmol/g protein, both much higher than [(1.0±0.3)mmol/g protein and (0.8±0.1)mmol/g protein, P<0.01] in the control, while in HFD/Nar-intervention group, they significantly decreased to [(2.1±0.4)mmol/g protein and (1.11±0.3)mmol/g protein, P<0.05]; KEGG enrichment analysis by transcriptome sequencing showed obvious impacts of naringin on nine pathways related to lipid metabolism, presenting with hepatic sterol regulatory element binding protein 1 (SREBP1), peroxisome proliferator-activated receptor-γ (PPAR-γ), thrombospondin receptor (CD36) and liver-type fatty acid-binding protein 1 (FABP1) down-regulation(P<0.05), and PPAR-α and recombinant carnitine palmitoyltransferase 1A (CPT-1A) up-regulation(P<0.05). Conclusion Naringin could significantly ameliorate hepatic lipid deposition, the mechanisms by which it work might be related to regulation of some gene expression and inhibit lipid uptake and synthesis, and accelerate fatty acid oxidation.

Key words: Non-alcoholic fatty liver diseases, Naringin, Sterol regulatory element binding protein 1, Peroxisome proliferator-activated receptor-γ, Liver-type fatty acid-binding protein 1, Recombinant carnitine palmitoyltransferase 1A, Mice

贾纪会, 张译之, 林静, 兰佳庆, 陈煜, 段钟平, 张晓慧. 柚皮苷调节NAFLD小鼠脂代谢紊乱机制研究^*[J]. 实用肝脏病杂志, 2024, 27(6): 816-819.

Jia Jihui, Zhang Yizhi, Lin Jing, et al. Down-regulation of hepatic SREBP1 and PPAR-γ expression by naringin in mice with high-fat diet-induced NAFLD[J]. Journal of Practical Hepatology, 2024, 27(6): 816-819.

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柚皮苷调节NAFLD小鼠脂代谢紊乱机制研究^*

Down-regulation of hepatic SREBP1 and PPAR-γ expression by naringin in mice with high-fat diet-induced NAFLD

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