Zhenyu Wang, Mingyang Zhang, Miao Chen, Shuning Fu, Yang Zhang, Mengyue Chen, Xiong Z Ruan, Yaxi Chen
{"title":"Daytime-restricted feeding induces lean MAFLD in high-fat diet-fed mice by upregulating CD36-mediated lipid accumulation.","authors":"Zhenyu Wang, Mingyang Zhang, Miao Chen, Shuning Fu, Yang Zhang, Mengyue Chen, Xiong Z Ruan, Yaxi Chen","doi":"10.1016/j.jlr.2025.100853","DOIUrl":null,"url":null,"abstract":"<p><p>Time-restricted feeding (TRF) may aid in weight loss and improve metabolic health; however, its long-term effects and applicability to all individuals remain unclear. This study investigated the impact of different dietary patterns on hepatic metabolism by subjecting mice to either a normal chow diet or a high-fat diet, allowing for ad libitum feeding, daytime restrictive feeding (DRF), or nighttime restrictive feeding (NRF). Using metabolic cages to assess energy intake, we found that the fuel utilization rhythms of DRF mice were disrupted compared to ad libitum-fed mice. Mice on normal chow DRF exhibited only dyslipidemia, while those on high-fat DRF developed lean metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by more pronounced dyslipidemia, weight loss, and hepatic lipid accumulation. RNA seq revealed that CD36 plays a crucial role in the development of lean MAFLD induced by high-fat DRF by inhibiting AMPK phosphorylation, disrupting the balance between lipogenesis and oxidation. Mechanistic validation was performed in CD36 liver-specific knockout mice and Liposomal nanoparticles injection models. These findings provide new insights into the potential mechanisms linking feeding patterns to lean MAFLD. Additionally, CD36 emerges as a potential therapeutic target for high-fat-induced lean MAFLD. Clarifying the relationship between DRF and lean MAFLD may inform guidelines for specific populations, such as individuals practicing intermittent fasting or those working night shifts, while also suggesting potential therapeutic strategies for clinical management.</p>","PeriodicalId":16209,"journal":{"name":"Journal of Lipid Research","volume":" ","pages":"100853"},"PeriodicalIF":5.0000,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Lipid Research","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1016/j.jlr.2025.100853","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Time-restricted feeding (TRF) may aid in weight loss and improve metabolic health; however, its long-term effects and applicability to all individuals remain unclear. This study investigated the impact of different dietary patterns on hepatic metabolism by subjecting mice to either a normal chow diet or a high-fat diet, allowing for ad libitum feeding, daytime restrictive feeding (DRF), or nighttime restrictive feeding (NRF). Using metabolic cages to assess energy intake, we found that the fuel utilization rhythms of DRF mice were disrupted compared to ad libitum-fed mice. Mice on normal chow DRF exhibited only dyslipidemia, while those on high-fat DRF developed lean metabolic dysfunction-associated fatty liver disease (MAFLD), characterized by more pronounced dyslipidemia, weight loss, and hepatic lipid accumulation. RNA seq revealed that CD36 plays a crucial role in the development of lean MAFLD induced by high-fat DRF by inhibiting AMPK phosphorylation, disrupting the balance between lipogenesis and oxidation. Mechanistic validation was performed in CD36 liver-specific knockout mice and Liposomal nanoparticles injection models. These findings provide new insights into the potential mechanisms linking feeding patterns to lean MAFLD. Additionally, CD36 emerges as a potential therapeutic target for high-fat-induced lean MAFLD. Clarifying the relationship between DRF and lean MAFLD may inform guidelines for specific populations, such as individuals practicing intermittent fasting or those working night shifts, while also suggesting potential therapeutic strategies for clinical management.
期刊介绍:
The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.