摘要
目的探究高脂饮食(high-fat diet,HFD)条件下,隔日禁食(every-other-day fasting,EODF)对小鼠腹沟股白色脂肪组织(inguinal white adipose tissue,iWAT)代谢谱的规律性变化并揭示差异代谢物及代谢通路,从而为改善肥胖提供潜在的候选代谢物。方法将8周龄的雄性C57BL/6J小鼠随机分为HFD自由进食组(AL组)和HFD结合EODF组。小鼠喂养8周后,取iWAT进行代谢组学和转录组学检测并分析。结果EODF显著改善HFD诱导的小鼠肥胖。代谢组学显示iWAT中氨基酸、碳水化合物和有机酸占比76.03%,且71种差异代谢物主要富集于氨基酰⁃tRNA合成、中性/芳香族氨基酸代谢及精脯氨酸代谢。基因本体(gene ontology,GO)分析与基因富集分析(gene set enrichment analysis,GSEA)表明EODF处理诱导的差异基因在氨基酸跨质膜输入通路和细胞核糖体组分显著富集。此外,EODF显著促进iWAT中的糖代谢,影响糖酵解初始阶段,抑制磷酸戊糖途径,且增强三羧酸循环,促进线粒体氧化磷酸化进程。结论EODF可改善小鼠肥胖并影响iWAT氨基酸和糖相关代谢通路,提示其可能通过增强能量消耗来维持代谢稳态。
Objective To investigate the metabolic profiles changes of inguinal white adipose tissue(iWAT)in mice induced by every-other-day fasting(EODF)under a high-fat diet(HFD)conditions,and to identify differential metabolites and metabolic pathways to provide potential candidate metabolites for obesity intervention.Methods Eight-week-old male C57BL/6J mice were randomly assigned to either an ad libitum HDF feeding group(AL group)or an HFD with EODF group.After 8 weeks,iWAT was collected for metabolomic and transcriptomic analyses.Results EODF significantly alleviated HFD-induced obesity in mice.Metabolomics analysis showed that amino acids,carbohydrates,and organic acids comprised 76.03%of the detected metabolites in iWAT.A total of 71 differential metabolites were identified,primarily enriched in aminoacyl-tRNA biosynthesis,neutral/aromatic amino acid metabolism,and arginine/proline metabolism.Gene ontology and gene set enrichment analysis enrichment analyses demonstrated that EODF treatment-induced differential genes were significantly enriched in amino acid import across plasma membrane and ribosome cellular components.In addition,EODF significantly promoted glucose metabolism in iWAT,influenced the initial phase of glycolysis,inhibited the pentose phosphate pathway,enhanced the tricarboxylic acid cycle,and promoted the mitochondrial oxidative phosphorylation.Conclusion EODF ameliorated obesity in mouse and remodeled amino acid and carbohydrate-related metabolic pathways in their iWAT,suggesting that it may maintain metabolic homeostasis by enhancing energy expenditure.
作者
王宁
李洋
WANG Ning;LI Yang(Department of Pharmacology,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;Key Laboratory of Metabolism and Molecular Medicine,Ministry of Education,School of Basic Medical Sciences,Fudan University,Shanghai 200032,China;State Key Laboratory of Brain Function and Disorders,Ministry of Education Frontiers Center for Brain Science,Institutes of Brain Science,Fudan University,Shanghai 200032,China)
出处
《复旦学报(医学版)》
北大核心
2026年第1期13-25,共13页
Fudan University Journal of Medical Sciences
基金
国家自然科学基金(92057103)。
