Bushman Theresa, Lin Te-Yueh, Jin Xuenan, Fu Qin, Zhang Sheng, Chen Xiaoli
Department of Food Science and Nutrition University of Minnesota-Twin Cities St. Paul Minnesota USA.
Proteomics and Metabolomics Facility Cornell University Ithaca New York USA.
J Extracell Biol. 2025 Jun 23;4(6):e70062. doi: 10.1002/jex2.70062. eCollection 2025 Jun.
Extracellular vesicle (EV) secretion and cargo composition are dysregulated in metabolic diseases. This study aimed to investigate how changes in serum EV concentration and protein composition reflect the metabolic effects of a high-fat diet (HFD) and time-restricted feeding (TRF), with a particular focus on adipocyte-derived EVs (Ad-EVs) in circulation. Mice were fed an HFD for 18 weeks prior to being placed either ad libitum or on a TRF for an additional 10 weeks. Mice on a normal chow ad libitum served as the control. The TRF group had food available for 10 h and fasted for 14 h per day. The serum EV size profile and amount displayed sex- and age-dependent changes in HFD-induced obesity, with age reducing EV amounts. HFD decreased small EV populations and increased larger EV populations, while TRF reversed these changes. Quantitative proteomic analysis showed that the abundance and composition of EV proteins changed in response to both acute stimulation with lipopolysaccharides (LPS) and HFD. Gene ontology analysis identified specific sets of EV proteins and their involved biological processes, reflecting the effect of LPS and HFD, as well as the reversal effect of TRF on metabolic and inflammatory pathways. EV proteins altered by HFD and those reversed by TRF had low protein overlap but significant functional overlap in biological processes. TRF activated the PPAR signalling pathway and the AKT-mTOR signalling pathway. The most significant impacts of HFD and TRF were observed on lipoprotein and carbohydrate metabolism, the complement system, and neutrophil degranulation. Additionally, we showed that serum Ad-EVs respond dynamically to HFD and TRF. Our findings suggest that EVs play a role in diet-induced metabolic and inflammatory responses, with changes in circulating EVs, particularly Ad-EVs, reflecting metabolic adaptations to dietary exposures and interventions.
细胞外囊泡（EV）的分泌及货物组成在代谢性疾病中失调。本研究旨在探究血清EV浓度和蛋白质组成的变化如何反映高脂饮食（HFD）和限时进食（TRF）的代谢效应，特别关注循环中脂肪细胞衍生的EV（Ad-EV）。小鼠先喂食HFD 18周，然后随意进食或进行TRF，持续10周。随意进食正常饲料的小鼠作为对照。TRF组每天有10小时可进食，禁食14小时。血清EV大小分布和数量在HFD诱导的肥胖中呈现性别和年龄依赖性变化，年龄增长会使EV数量减少。HFD减少了小EV群体，增加了大EV群体，而TRF则逆转了这些变化。定量蛋白质组学分析表明，EV蛋白的丰度和组成会因脂多糖（LPS）急性刺激和HFD而发生变化。基因本体分析确定了特定的EV蛋白组及其涉及的生物学过程，反映了LPS和HFD的影响，以及TRF对代谢和炎症途径的逆转作用。受HFD改变且被TRF逆转的EV蛋白在蛋白质水平上重叠较少，但在生物学过程中存在显著的功能重叠。TRF激活了PPAR信号通路和AKT-mTOR信号通路。HFD和TRF对脂蛋白和碳水化合物代谢、补体系统以及中性粒细胞脱颗粒的影响最为显著。此外，我们表明血清Ad-EV对HFD和TRF有动态反应。我们的研究结果表明，EV在饮食诱导的代谢和炎症反应中起作用，循环EV的变化，特别是Ad-EV的变化，反映了对饮食暴露和干预的代谢适应。
