Daytime-restricted feeding induces lean MAFLD in high-fat diet-fed mice by upregulating CD36-mediated lipid accumulation.

IF 5 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zhenyu Wang, Mingyang Zhang, Miao Chen, Shuning Fu, Yang Zhang, Mengyue Chen, Xiong Z Ruan, Yaxi Chen
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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.

白天限制喂养通过上调cd36介导的脂质积累,诱导高脂饮食喂养小鼠的瘦型MAFLD。
限时喂养(TRF)可能有助于减肥和改善代谢健康;然而,其长期效果和对所有个体的适用性仍不清楚。本研究调查了不同饮食模式对肝脏代谢的影响,通过给小鼠正常饮食或高脂肪饮食,允许随意喂养,白天限制性喂养(DRF)或夜间限制性喂养(NRF)。使用代谢笼来评估能量摄入,我们发现与自由喂养的小鼠相比,DRF小鼠的燃料利用节律被打乱。正常饮食DRF的小鼠仅表现出血脂异常,而高脂肪DRF的小鼠则出现瘦代谢功能障碍相关的脂肪性肝病(MAFLD),其特征是更明显的血脂异常、体重减轻和肝脏脂质积累。RNA测序结果显示,CD36通过抑制AMPK磷酸化,破坏脂肪生成和氧化之间的平衡,在高脂DRF诱导的瘦肉型MAFLD的发展中起着至关重要的作用。在CD36肝脏特异性敲除小鼠和脂质体纳米颗粒注射模型中进行了机制验证。这些发现提供了新的见解,将喂养模式与精益MAFLD联系起来的潜在机制。此外,CD36成为高脂肪诱导的瘦型MAFLD的潜在治疗靶点。澄清DRF和精益mld之间的关系可以为特定人群提供指导,例如间歇性禁食或夜班工作的个体,同时也为临床管理提供潜在的治疗策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
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.
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