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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

Received: 　　Accepted:

Corresponding author: 张瑾　　E-mail: zhangjin7688@163.com

Citing This Article：

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).