脂质体特征可区分猪非酒精性脂肪性肝炎进展过程中肝脏的细微变化。

IF 3.9 3区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-04-01 Epub Date: 2024-02-20 DOI:10.1152/ajpgi.00264.2023
Luis V Herrera-Marcos, Roberto Martínez-Beamonte, Carmen Arnal, Cristina Barranquero, Juan J Puente-Lanzarote, José M Lou-Bonafonte, Gonzalo Gonzalo-Romeo, Gabriele Mocciaro, Benjamin Jenkins, Joaquín C Surra, María J Rodríguez-Yoldi, Víctor Alastrué-Vera, Jesús Letosa, Agustín García-Gil, Antonio Güemes, Albert Koulman, Jesús Osada
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引用次数: 0

摘要

最近,一种富含饱和脂肪、果糖、胆固醇和胆酸盐以及缺乏胆碱和蛋氨酸的日粮在普通猪品系中引起了非酒精性脂肪性肝炎(NASH)。本研究的目的是描述伴随 NASH 进展的肝脏和血浆脂质体变化的特征,以及通过将猪改回饲料而逆转 NASH 的过程。一个月的极端脂肪饮食足以诱发猪NASH。使用液相色谱-质谱联用技术的脂质组学平台分析了 467 种脂质。七种肝磷脂[PC(30:0)、PC(32:0)、PC(33:0)、PC(33:1)、PC(34:0)、PC(34:3)和PC(36:2)]显著区分了饮食暴露的时间,PC(30:0)、PC(33:0)、PC(33:1)和PC(34:0)在恢复期表现出快速适应。CS、MAT1A 和 SPP1 这三个转录本显示出与肝甘油三酯和 PC(33:0) 相关的显著变化。血浆脂质组学显示,这些物种[FA 16:0、FA 18:0、LPC(17:1)、PA(40:5)、PC(37:1)、TG(45:0)、TG(47:2)和 TG(51:0)]能够区分饮食暴露的时间。其中,FA 16:0、FA 18:0、LPC(17:1)和 PA(40:5)改变了逆转阶段的趋势。血浆低密度脂蛋白胆固醇和IL12P40是研究NASH进展的良好参数,但其能力被肝脏[PC(33:0)、PC(33:1)和PC(34:0)]或血浆脂质[FA 16:0、FA 18:0和LPC(17:1)]物种所超越。综合来看,这些脂质种类可作为该模型中 NASH 进展和消退过程中代谢变化的生物标记物。这些脂质变化表明,NASH 的发展也会影响外周脂质代谢。
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Lipidomic signatures discriminate subtle hepatic changes in the progression of porcine nonalcoholic steatohepatitis.

Recently, the development of nonalcoholic steatohepatitis (NASH) in common strains of pigs has been achieved using a diet high in saturated fat, fructose, cholesterol, and cholate and deficient in choline and methionine. The aim of the present work was to characterize the hepatic and plasma lipidomic changes that accompany the progression of NASH and its reversal by switching pigs back to a chow diet. One month of this extreme steatotic diet was sufficient to induce porcine NASH. The lipidomic platform using liquid chromatography-mass spectrometry analyzed 467 lipid species. Seven hepatic phospholipids [PC(30:0), PC(32:0), PC(33:0), PC(33:1), PC(34:0), PC(34:3) and PC(36:2)] significantly discriminated the time of dietary exposure, and PC(30:0), PC(33:0), PC(33:1) and PC(34:0) showed rapid adaptation in the reversion period. Three transcripts (CS, MAT1A, and SPP1) showed significant changes associated with hepatic triglycerides and PC(33:0). Plasma lipidomics revealed that these species [FA 16:0, FA 18:0, LPC(17:1), PA(40:5), PC(37:1), TG(45:0), TG(47:2) and TG(51:0)] were able to discriminate the time of dietary exposure. Among them, FA 16:0, FA 18:0, LPC(17:1) and PA(40:5) changed the trend in the reversion phase. Plasma LDL-cholesterol and IL12P40 were good parameters to study the progression of NASH, but their capacity was surpassed by hepatic [PC(33:0), PC(33:1), and PC(34:0)] or plasma lipid [FA 16:0, FA 18:0, and LPC(17:1)] species. Taken together, these lipid species can be used as biomarkers of metabolic changes in the progression and regression of NASH in this model. The lipid changes suggest that the development of NASH also affects peripheral lipid metabolism.NEW & NOTEWORTHY A NASH stage was obtained in crossbred pigs. Hepatic [PC(33:0), PC(33:1) and PC(34:0)] or plasma [FA 16:0, FA 18:0 and LPC(17:1)] species were sensitive parameters to detect subtle changes in development and regression of nonalcoholic steatohepatitis (NASH). These findings may delineate the liquid biopsy to detect subtle changes in progression or in treatments. Furthermore, phospholipid changes according to the insult-inducing NASH may play an important role in accepting or rejecting fatty livers in transplantation.

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来源期刊
CiteScore
9.40
自引率
2.20%
发文量
104
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Gastrointestinal and Liver Physiology publishes original articles pertaining to all aspects of research involving normal or abnormal function of the gastrointestinal tract, hepatobiliary system, and pancreas. Authors are encouraged to submit manuscripts dealing with growth and development, digestion, secretion, absorption, metabolism, and motility relative to these organs, as well as research reports dealing with immune and inflammatory processes and with neural, endocrine, and circulatory control mechanisms that affect these organs.
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