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成人代谢功能障碍相关脂肪性肝炎肝脏脂质组学特征的综合分析——一项初步研究

A Comprehensive Analysis of Liver Lipidomics Signature in Adults with Metabolic Dysfunction-Associated Steatohepatitis-A Pilot Study.

作者信息

Mouskeftara Thomai, Kalopitas Georgios, Liapikos Theodoros, Arvanitakis Konstantinos, Theocharidou Eleni, Germanidis Georgios, Gika Helen

机构信息

Laboratory of Forensic Medicine & Toxicology, Department of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Division of Gastroenterology and Hepatology, 1st Department of Internal Medicine, AHEPA University Hospital, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

出版信息

Int J Mol Sci. 2024 Dec 5;25(23):13067. doi: 10.3390/ijms252313067.

DOI:10.3390/ijms252313067
PMID:39684777
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11642547/
Abstract

Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) is the most common chronic liver disorder in Western countries, encompassing a range of conditions from steatosis to Metabolic Dysfunction-Associated Steatohepatitis (MASH), which can potentially progress to cirrhosis. Lipidomics approaches have revealed significant alterations in the hepatic lipidome associated with both steatosis and steatohepatitis, with these changes correlating with disease manifestation. While the transition from steatosis to MASH remains poorly understood, recent research indicates that both the quantity and quality of deposited lipids play a pivotal role in MASLD progression. In our study, we utilized untargeted and targeted analyses to identify intact lipids and fatty acids in liver biopsies from healthy controls and MASLD patients, categorized based on their histological findings. In total, 447 lipid species were identified, with 215 subjected to further statistical analysis. Univariate and multivariate analyses revealed alterations in triglyceride species and fatty acids, including FA 16:0, FA 16:1, FA 18:3 n6, the sum of MUFA, and the Δ9-desaturase activity ratio. This research provides insights into the connection between dysregulated lipid metabolism in the progression of MASLD, supporting previous findings. Further studies on lipid metabolism could improve risk assessment methods, particularly given the current limited understanding of the transition from steatosis to MASH.

摘要

代谢功能障碍相关脂肪性肝病(MASLD)是西方国家最常见的慢性肝脏疾病,涵盖了从脂肪变性到代谢功能障碍相关脂肪性肝炎(MASH)的一系列病症,后者有可能进展为肝硬化。脂质组学方法已揭示出与脂肪变性和脂肪性肝炎相关的肝脏脂质组有显著改变,这些变化与疾病表现相关。虽然从脂肪变性到MASH的转变仍知之甚少,但最近的研究表明,沉积脂质的数量和质量在MASLD进展中都起着关键作用。在我们的研究中,我们利用非靶向和靶向分析来鉴定健康对照和MASLD患者肝脏活检中的完整脂质和脂肪酸,并根据组织学结果进行分类。总共鉴定出447种脂质种类,其中215种进行了进一步的统计分析。单变量和多变量分析揭示了甘油三酯种类和脂肪酸的改变,包括FA 16:0、FA 16:1、FA 18:3 n6、单不饱和脂肪酸总和以及Δ9-去饱和酶活性比率。这项研究为MASLD进展过程中脂质代谢失调之间的联系提供了见解,支持了先前的研究结果。鉴于目前对从脂肪变性到MASH转变的了解有限,对脂质代谢的进一步研究可能会改善风险评估方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/1d217e536b5a/ijms-25-13067-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/3f61f42ec4b9/ijms-25-13067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/388ba4a62bc5/ijms-25-13067-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/3e33edfdd882/ijms-25-13067-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/1d217e536b5a/ijms-25-13067-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/3f61f42ec4b9/ijms-25-13067-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/388ba4a62bc5/ijms-25-13067-g002a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/3e33edfdd882/ijms-25-13067-g003a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b0d0/11642547/1d217e536b5a/ijms-25-13067-g004a.jpg

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本文引用的文献

1
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2
Predicting Non-Alcoholic Steatohepatitis: A Lipidomics-Driven Machine Learning Approach.预测非酒精性脂肪性肝炎:一种基于脂质组学的机器学习方法。
Int J Mol Sci. 2024 May 29;25(11):5965. doi: 10.3390/ijms25115965.
3
EASL-EASD-EASO Clinical Practice Guidelines on the management of metabolic dysfunction-associated steatotic liver disease (MASLD).
EASL-EASD-EASO 临床实践指南:代谢功能障碍相关脂肪性肝病(MASLD)的管理。
J Hepatol. 2024 Sep;81(3):492-542. doi: 10.1016/j.jhep.2024.04.031. Epub 2024 Jun 7.
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Lipidomic Analysis of Liver and Adipose Tissue in a High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease Mice Model Reveals Alterations in Lipid Metabolism by Weight Loss and Aerobic Exercise.高脂饮食诱导的非酒精性脂肪肝疾病小鼠模型的肝脏和脂肪组织脂质组学分析揭示了减肥和有氧运动对脂代谢的影响。
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Plasma Lipids Profile in the Prediction of Non-Alcoholic Steatohepatitis in Adults: A Case-Control Study.血浆脂质谱在成人非酒精性脂肪性肝炎预测中的作用:一项病例对照研究。
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AASLD Practice Guidance on the clinical assessment and management of nonalcoholic fatty liver disease.美国肝病研究学会非酒精性脂肪性肝病临床评估与管理实践指南
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