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非靶向代谢组学揭示 AQP9 在小鼠非酒精性脂肪肝疾病中的作用。

Untargeted metabolomics reveals the role of AQP9 in nonalcoholic fatty liver disease in a mice model.

机构信息

Department of Human Anatomy and Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.

Department of Liver Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College (PUMC) Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

出版信息

Int J Biol Macromol. 2022 Oct 31;219:864-875. doi: 10.1016/j.ijbiomac.2022.08.023. Epub 2022 Aug 10.

Abstract

Previous studies have shown that AQP9 plays an important role in energy metabolism in nonalcoholic fatty liver disease (NAFLD). Recently, metabolomic analyses were used to determine the slight changes in metabolic profiles and helped to understand the disease progression, therapeutic intervention of NAFLD. A mouse model of NAFLD was established with a high-fat diet (HFD), and Aqp9 knockout mice were constructed. Untargeted metabolomics techniques were used to evaluate the potential mechanism of the effect of AQP9 in NAFLD. The results indicated that AQP9 plays a regulatory role in the occurrence of NAFLD. Moreover, a total of 220 candidate biomarkers were screened and identified. Cluster analysis and enrichment analysis of differential metabolites indicated that fatty acid biosynthesis was mainly disturbed when compared against the control group, which was mitigated by knockout of Aqp9. These results show that untargeted metabolomics help to understand the effects of AQP9 in NAFLD.

摘要

先前的研究表明,水通道蛋白 9(AQP9)在非酒精性脂肪性肝病(NAFLD)的能量代谢中发挥重要作用。最近,代谢组学分析被用于确定代谢谱的细微变化,有助于了解疾病的进展和 NAFLD 的治疗干预。通过高脂肪饮食(HFD)建立了 NAFLD 小鼠模型,并构建了 Aqp9 敲除小鼠。非靶向代谢组学技术用于评估 AQP9 在 NAFLD 中的作用的潜在机制。结果表明,AQP9 在 NAFLD 的发生中起调节作用。此外,筛选和鉴定了 220 种候选生物标志物。与对照组相比,差异代谢物的聚类分析和富集分析表明,脂肪酸生物合成主要受到干扰,而 Aqp9 敲除则减轻了这种干扰。这些结果表明,非靶向代谢组学有助于了解 AQP9 在 NAFLD 中的作用。

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