Alternate-day fasting prevents non-alcoholic fatty liver disease and working memory impairment in diet-induced obese mice

Wentong Zhang; Jun Wang; Luanfeng Wang; Renjie Shi; Chuanqi Chu; Zhiling Shi; Pujie Liu; Yitong Li; Xuebo Liu; Zhigang Liu

doi:10.1016/j.jnutbio.2022.109146

Alternate-day fasting prevents non-alcoholic fatty liver disease and working memory impairment in diet-induced obese mice

J Nutr Biochem. 2022 Dec:110:109146. doi: 10.1016/j.jnutbio.2022.109146. Epub 2022 Aug 29.

Authors

Wentong Zhang¹, Jun Wang², Luanfeng Wang³, Renjie Shi³, Chuanqi Chu³, Zhiling Shi³, Pujie Liu³, Yitong Li⁴, Xuebo Liu³, Zhigang Liu⁵

Affiliations

¹ Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi Province, China; Zhejiang Provincial Key Laboratory of Pancreatic Disease, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, China.
² Department of Digestive Diseases, Xijing Hospital, Xi'an, Shaanxi Province, China.
³ Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi Province, China.
⁴ Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA.
⁵ Laboratory of Functional Chemistry and Nutrition of Food, College of Food Science and Engineering, Northwest A&F University, Yangling, Shaanxi Province, China; Department of Food Science, College of Agriculture and Life Sciences, Cornell University, Ithaca, New York, USA. Electronic address: Zhigangliu@nwsuaf.edu.cn.

PMID: 36049672
DOI: 10.1016/j.jnutbio.2022.109146

Abstract

Alternate-day fasting (ADF) regimen has been reported to alleviate obesity and insulin resistance. However, the effects of ADF on preventing diet-induced non-alcoholic fatty liver disease (NAFLD) and related cognitive deficits are still elusive. In the present study, a high-fat diet (HFD)-induced obese (DIO) C57BL/6 mouse model was established. Mice were treated with a 4-week long ADF regimen and/or switching the diet to a standard diet. ADF reduced lipid accumulation, activated AMPK/ULK1 signaling, and suppressed the phosphorylation of mTOR. Also, ADF inhibited lipid accumulation and inflammatory responses in the white adipose tissue and down-regulated expressions of PPAR-γ and cytokines. Moreover, ADF improved the working memory and synaptic structure in the DIO mice and upregulated PSD-95 and BDNF in the hippocampus. ADF reduced oxidative stress and microglial over-activation in the CNS. These results suggest that ADF attenuates NAFLD development in the liver of DIO mice, which is related to the mediating effects of ADF on autophagy and energy metabolism. ADF also enhanced cognitive function, which could be partly explained by the down-regulated peripheral inflammatory responses. This study indicates that ADF could be a promising intervention for alleviating NAFLD development and cognitive decline.

Keywords: Alternate-day fasting; Autophagy; Diet-induced obesity; Memory impairment; NAFLD.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diet, High-Fat / adverse effects
Fasting
Lipid Metabolism
Lipids
Liver / metabolism
Memory, Short-Term
Mice
Mice, Inbred C57BL
Mice, Obese
Non-alcoholic Fatty Liver Disease* / etiology
Non-alcoholic Fatty Liver Disease* / metabolism
Non-alcoholic Fatty Liver Disease* / prevention & control
Obesity / metabolism

Substances

Lipids