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长期间歇性禁食诱导小鼠肝脏脂质异常积聚

龚鹏飞^1,2, 江祖荣², 黄鑫², 王思思², 李汉兵², 彭永佳², 张瑾^2,*

¹浙江工业大学药学院，杭州 310014；²嘉兴学院生物与化学工程学院，嘉兴 314001

摘要

短期间歇性禁食有利于非酒精性脂肪肝病患者控制体重，但长期间歇性禁食的影响还不明确。本研究以C57BL/6N小鼠为模型，采用4个月隔日禁食方式研究长期间歇性禁食对小鼠健康及肝脏脂质代谢的影响。结果显示，与自由采食组相比，隔日禁食组小鼠的体重降低，饲料转化率增加，肝脏指数增加，病理切片分析发现肝脏甘油三酯含量显著增加；qRT-PCR分析发现肝脏脂代谢标志基因Pparγ和Atgl的表达显著升高(P < 0.05)；Western blot分析发现微管相关蛋白LC3-II/LC3-I比值升高(P < 0.05)，自噬接头蛋白p62 (SQSTM1)丰度降低(P < 0.05)，自噬信号正调控关键因子AMPK磷酸化升高(P < 0.05)，负调控因子mTOR磷酸化降低(P < 0.05)，表明肝细胞自噬活性增强。综上所述，4个月隔日禁食可引起健康小鼠肝脏中积累过多甘油三酯，同时显著降低mTOR磷酸化水平并提高自噬水平。

关键词： 长期隔日禁食; 肝脂质积累; 脂代谢; 自噬

Long-term intermittent fasting induces abnormal lipid accumulation in mouse liver

GONG Peng-Fei^1,2, JIANG Zu-Rong², HUANG Xin², WANG Si-Si², LI Han-Bing², PENG Yong-Jia², ZHANG Jin^2,*

¹College of Pharmacy, Zhejiang University of Technology, Hangzhou 310014, China；²School of Biological and Chemical Engineering, Jiaxing University, Jiaxing 314001, China

Abstract

Short-term intermittent fasting (IF) is beneficial to weight control in patients with nonalcoholic fatty liver disease, but the impact of long-term IF is not clear. In this study, healthy C57BL/6N mice with 4-month alternate day fasting (ADF) were used to study the effects of long-term IF on systemic and liver lipid metabolism. The results showed that, compared with the Ad Libitum group, the weight and food conversion rate of mice in the ADF group were markedly decreased and increased respectively, and the liver index and the liver content of triglyceride were significantly increased by pathological examination. qRT-PCR analysis revealed that the mRNA expression of the lipogenesis gene Pparγ and lipolysis gene Atgl was up-regulated in the ADF group (P < 0.05). Western blot analysis showed that the ratio of microtubule associated protein LC3-II/LC3-I was increased, while the abundance of autophagy adaptor protein p62 was decreased in the ADF group. In addition, autophagy signal positive regulation key factor AMPK phosphorylation was increased (P < 0.05), and negative regulation factor mTOR phosphorylation was decreased (P < 0.05) in the ADF group, indicating that hepatocyte autophagy activity was elevated. Taken together, ADF for 4 months results in an excessive liver triglyceride accumulation, accompanied by a marked decrease in liver mTOR phosphorylation and a significant increase in hepatic autophagy.

Key words: long-term alternative day fasting; hepatic lipid accumulation; lipid metabolism; autophagy

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通讯作者：张瑾　　E-mail: zhangjin7688@163.com

引用本文：

龚鹏飞, 江祖荣, 黄鑫, 王思思, 李汉兵, 彭永佳, 张瑾. 长期间歇性禁食诱导小鼠肝脏脂质异常积聚[J]. 生理学报 2022; 74 (6): 962-969.

GONG Peng-Fei, JIANG Zu-Rong, HUANG Xin, WANG Si-Si, LI Han-Bing, PENG Yong-Jia, ZHANG Jin. Long-term intermittent fasting induces abnormal lipid accumulation in mouse liver. Acta Physiol Sin 2022; 74 (6): 962-969 (in Chinese with English abstract).