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《工程(英文)》 >> 2022年 第9卷 第2期 doi: 10.1016/j.eng.2020.05.023

功能代谢组学揭示黄芪多糖通过2-羟基丁酸改善肥胖小鼠的脂质代谢

a Institute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
b Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
c Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai 200233, China
d University of Hawaii Cancer Center, Honolulu, HI 96813, USA

# These authors contributed equally to this work.

收稿日期: 2019-12-31 修回日期: 2020-05-16 录用日期: 2020-05-25 发布日期: 2020-10-16

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摘要

多糖广泛存在于草本植物中,具有多种活性,特别是具有免疫调节作用和改善代谢紊乱的作用。然而,其潜在机制还没有被很好地诠释。功能代谢组学越来越多地被用于通过鉴定具有特定功能的代谢产物来研究多糖对宿主的系统性影响。本研究采用功能代谢组学策略,探讨黄芪多糖(Astragalus polysaccharide, APS)代谢获益的潜在机制。在为期8 周的高脂肪饮食(high-fat diet, HFD)喂养的肥胖小鼠中测定了APS的作用。然后,进行基于气相色谱-飞行时间质谱(gas chromatography-time-of-flight mass spectrometry, GC-TOFMS)的非靶向代谢组学分析血清和肝组织,并进行基于液相色谱- 串联质谱(liquid chromatography-tandem mass spectrometry, LC-MS/MS)的靶向代谢组学分析。使用体外和体内代谢紊乱模型测试了代谢产物的潜在功能。我们的结果首次证实了APS对肥胖小鼠的代谢益处。然后,代谢组学分析显示,补充APS 可逆转HFD 诱导的代谢变化,并确定2-羟基丁酸(2-hydroxybutyric acid, 2-HB)是APS活性的潜在功能性代谢产物,该代谢物被HFD显著降低,并被APS逆转。进一步研究表明,2-HB可抑制油酸(oleic acid, OA)诱导的甘油三酯(triglyceride, TG)累积。还发现其可刺激肝细胞中脂质降解蛋白的表达和3T3-L1 细胞中的TG脂解。此外,在高脂肪和高蔗糖(high-fat and high-sucrose, HFHS)喂养的小鼠中发现2-HB可降低血清TG并调节参与脂质降解的蛋白质。总之,我们的研究表明,APS的代谢
益处至少部分归因于2-HB 的产生,2-HB 在体外和体内均可调节脂质代谢。我们的结果同样证实,功能代谢组学在研究植物多糖系统益处的潜在机制方面是切实可行的。

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