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单独间歇性禁食或间歇性禁食联合胰高血糖素样肽 - 1 受体激动剂对非酒精性脂肪肝大鼠的蛋白质组学分析

 

Authors Shao Y , Xu S , Ma Y , Zhang J, Guo X, Zhang T , Yuan G 

Received 17 July 2025

Accepted for publication 29 October 2025

Published 5 November 2025 Volume 2025:18 Pages 4073—4083

DOI https://doi.org/10.2147/DMSO.S550262

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Jae Woong Sull

Yimin Shao,1 Shengya Xu,1 Yuanyuan Ma,2 Junqing Zhang,1 Xiaohui Guo,1 Tingting Zhang,1 Geheng Yuan1 

1Department of Endocrinology, Peking University First Hospital, Beijing, People’s Republic of China; 2Laboratory Animal Center, Peking University First Hospital, Beijing, People’s Republic of China

Correspondence: Tingting Zhang, Department of Endocrinology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +86 10 83575103, Fax +86 10 66552395, Email cathine@sina.com Geheng Yuan, Department of Endocrinology, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing, 100034, People’s Republic of China, Tel +86 10 83575103, Fax +86 10 66552395, Email 139197109@qq.com

Background: Intermittent fasting (IF) and glucagon-like peptide-1 receptor agonists (GLP-1RA) offer effective therapeutic options for nonalcoholic fatty liver disease (NAFLD). This study aimed to examine the effects of alternate-day fasting (ADF) alone and with liraglutide, and to explore the mechanisms behind each treatment.
Methods: To establish the model for NAFLD, Sprague-Dawley rats were given a high-fat diet for 25 weeks. Subsequently, the rats were assigned to the ADF, ADF combined with liraglutide (A+L), and control groups for an additional 5 weeks. Evaluations were performed on liver morphology, body weight, serum lipid profiles, insulin sensitivity, and liver proteomics.
Results: Compared to the control group, ADF alone demonstrated a reduction in body weight (37.1± 15.56 g vs − 20.68± 15.58 g, p< 0.05), food intake (0.30± 0.002 g/d/rat vs 0.18± 6.21 g/d/rat), blood lipid levels, and ALT concentration (139.0± 15.57 U/L vs 91.25± 41.9 U/L, p< 0.05), while also improving the NAFLD score. Furthermore, ADF in conjunction with liraglutide exhibited superior effects in reducing body weight (− 96.15± 15.78 g), food intake (− 10.25± 0.01 g/d/rat), triglyceride (17.53± 0.25 nmol/L), and LDL concentrations (6.93± 0.35mmol/L), as well as ameliorating insulin resistance and lowering the NAFLD score relative to the ADF group (p< 0.05). The proteomic analysis indicates that G protein-coupled receptor 39 (GPR39) and transmembrane protein 41b (Tmem41b) were significantly upregulated in the A+L group compared to the other two groups. Additionally, hydroxysteroid 17β-dehydrogenase 2 (HSD17B2) was significantly diminished in both the ADF and A+L groups relative to the control group.
Conclusion: Intermittent fasting, in conjunction with GLP-1RA, further enhances metabolic health in individuals with NAFLD as a result of obesity. This study provides support for forthcoming clinical trials and aims to establish new therapeutic targets in the context of NAFLD.

Keywords: intermittent fasting, non-alcoholic fatty liver disease, glucagon-like peptide-1, proteomic changes, obesity