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瘦素介导的代谢相关脂肪性肝病患者脂肪酸代谢的靶向代谢组学研究

Targeted metabolomics study of fatty-acid metabolism in lean metabolic-associated fatty liver disease patients.

作者信息

Sun Pei-Qi, Dong Wen-Min, Yuan Yi-Fu, Cao Qin, Chen Xiao-Yan, Guo Li-Li, Jiang Yuan-Ye

机构信息

Department of Gastroenterology, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200062, China.

Department of Pharmacy, Shanghai Pudong Hospital, Fudan University Pudong Medical Center, Shanghai 201399, China.

出版信息

World J Gastroenterol. 2024 Jul 21;30(27):3290-3303. doi: 10.3748/wjg.v30.i27.3290.

DOI:10.3748/wjg.v30.i27.3290
PMID:39086751
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11287418/
Abstract

BACKGROUND

The annual incidence of metabolic-associated fatty liver disease (MAFLD) in China has been increasing and is often overlooked owing to its insidious characteristics. Approximately 50% of the patients have a normal weight or are not obese. They are said to have lean-type MAFLD, and few studies of such patients are available. Because MAFLD is associated with abnormal lipid metabolism, lipid-targeted metabolomics was used in this study to provide experimental evidence for early diagnosis and pathogenesis.

AIM

To investigate the serum fatty-acid metabolic characteristics in lean-type MAFLD patients using targeted serum metabolomic technology.

METHODS

Between January and June 2022, serum samples were collected from MAFLD patients and healthy individuals who were treated at Shanghai Putuo District Central Hospital for serum metabolomics analysis. Principal component analysis and orthogonal partial least squares-discriminant analysis models were developed, and univariate analysis was used to screen for biomarkers of lean-type MAFLD and analyze metabolic pathways. UPLC-Q-Orbitrap/MS content determination was used to determine serum palmitic acid (PA), oleic acid (OA), linoleic acid (LA), and arachidonic acid (AA) levels in lean-type MAFLD patients.

RESULTS

Urea nitrogen and uric acid levels were higher in lean-type MAFLD patients than in healthy individuals ( < 0.05). Alanine transaminase and cholinesterase levels were higher in lean-type MAFLD patients than in healthy individuals ( < 0.01). The expression of high-density lipoprotein and apolipoprotein A-1 were lower in lean-type MAFLD patients than in healthy individuals ( < 0.05) and the expression of triglycerides and fasting blood glucose were increased ( < 0.01). A total of 65 biomarkers that affected the synthesis and metabolism of fatty acids were found with < 0.05 and variable importance in projection > 1". The levels of PA, OA, LA, and AA were significantly increased compared with healthy individuals.

CONCLUSION

The metabolic profiles of lean-type MAFLD patients and healthy participants differed significantly, yielding 65 identified biomarkers. PA, OA, LA, and AA exhibited the most significant changes, offering valuable clinical guidance for prevention and treatment of lean-type MAFLD.

摘要

背景

中国代谢相关脂肪性肝病(MAFLD)的年发病率一直在上升,由于其隐匿性特征,常被忽视。约50%的患者体重正常或不肥胖。他们被称为瘦型MAFLD患者,对此类患者的研究较少。由于MAFLD与脂质代谢异常有关,本研究采用脂质靶向代谢组学为早期诊断和发病机制提供实验依据。

目的

运用靶向血清代谢组学技术研究瘦型MAFLD患者的血清脂肪酸代谢特征。

方法

2022年1月至6月,收集在上海普陀区中心医院接受治疗的MAFLD患者和健康个体的血清样本进行血清代谢组学分析。建立主成分分析和正交偏最小二乘判别分析模型,并采用单变量分析筛选瘦型MAFLD的生物标志物并分析代谢途径。采用超高效液相色谱-四极杆-轨道阱质谱含量测定法测定瘦型MAFLD患者血清中棕榈酸(PA)、油酸(OA)、亚油酸(LA)和花生四烯酸(AA)水平。

结果

瘦型MAFLD患者的尿素氮和尿酸水平高于健康个体(P<0.05)。瘦型MAFLD患者的丙氨酸转氨酶和胆碱酯酶水平高于健康个体(P<0.01)。瘦型MAFLD患者的高密度脂蛋白和载脂蛋白A-1表达低于健康个体(P<0.05),甘油三酯和空腹血糖表达升高(P<0.01)。共发现65个影响脂肪酸合成和代谢的生物标志物,P<0.05且投影变量重要性>1”。与健康个体相比,PA、OA、LA和AA水平显著升高。

结论

瘦型MAFLD患者与健康参与者的代谢谱存在显著差异,共鉴定出65个生物标志物。PA、OA、LA和AA变化最为显著,为瘦型MAFLD的防治提供了有价值的临床指导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/5fd066fe3ef9/WJG-30-3290-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/b896ed69d77c/WJG-30-3290-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/e2831a90956c/WJG-30-3290-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/53a9c5e7e9d0/WJG-30-3290-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/5fd066fe3ef9/WJG-30-3290-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/6e6b8e0c3862/WJG-30-3290-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/eb01ab43f190/WJG-30-3290-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/66e8cbfdcf91/WJG-30-3290-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/d49f16f7b47c/WJG-30-3290-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/b896ed69d77c/WJG-30-3290-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/e2831a90956c/WJG-30-3290-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/53a9c5e7e9d0/WJG-30-3290-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a479/11287418/5fd066fe3ef9/WJG-30-3290-g008.jpg

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