新的蛋白质组特征可显示 MRI 评估的肝内脂肪状态和变化;DIRECT PLUS 临床试验。

IF 12.9 1区 医学 Q1 GASTROENTEROLOGY & HEPATOLOGY
Hepatology Pub Date : 2025-01-01 Epub Date: 2024-03-27 DOI:10.1097/HEP.0000000000000867
Dana T Goldberg, Anat Yaskolka Meir, Gal Tsaban, Ehud Rinott, Alon Kaplan, Hila Zelicha, Nora Klöting, Uta Ceglarek, Berend Iserman, Ilan Shelef, Philip Rosen, Matthias Blüher, Michael Stumvoll, Ohad Etzion, Meir J Stampfer, Frank B Hu, Iris Shai
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引用次数: 0

摘要

目的:我们在为期 18 个月的随机 DIRECT PLUS 试验(n=294)中证实,与其他两种健康饮食相比,地中海饮食(MED)补充了富含多酚的万凯浮萍、绿茶和核桃,并限制红肉/加工肉类,可显著减少肝内脂肪(IHF%),将非酒精性脂肪肝减少一半,而体重减轻情况相似。在此,我们研究了与IHF%相关的基线蛋白质组学特征,以及与生活方式干预引起的IHF%变化相关的蛋白质组学变化:我们通过质子磁共振波谱(H-MRS;正常-IHF%=5%)计算IHF%。我们对基线样本和 18 个月样本中的 95 种蛋白质组生物标志物进行了检测:参与者(年龄=51.3±10.8岁;89%为男性;体质指数=31.3±3.9 kg/m2)的18个月保留率为89.8%;83%进行了合格的后续蛋白质组测量,78%进行了后续H-MRS测量。基线时,39种候选蛋白与IHF%显著相关(FDRC结论:我们的研究结果表明,新的蛋白质组特征可显示 MRI 评估的肝内脂肪状态以及生活方式干预期间的变化。具体来说,CA5A、HAOX1 和 THBS2 蛋白质的变化与 IHF% 的变化独立相关,而 THBS2 蛋白质的变化在绿色-MED/高多酚饮食中更大。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Novel proteomic signatures may indicate MRI-assessed intrahepatic fat state and changes: The DIRECT PLUS clinical trial.

Background and aims: We demonstrated in the randomized 18-month DIRECT PLUS trial (n = 294) that a Mediterranean (MED) diet, supplemented with polyphenol-rich Mankai duckweed, green tea, and walnuts and restricted in red/processed meat, caused substantial intrahepatic fat (IHF%) loss compared with 2 other healthy diets, reducing NAFLD by half, regardless of similar weight loss. Here, we investigated the baseline proteomic profile associated with IHF% and the changes in proteomics associated with IHF% changes induced by lifestyle intervention.

Approach and results: We calculated IHF% by proton magnetic resonance spectroscopy (normal IHF% <5% and abnormal IHF% ≥5%). We assayed baseline and 18-month samples for 95 proteomic biomarkers.Participants (age = 51.3 ± 10.8 y; 89% men; and body mass index = 31.3 ± 3.9 kg/m 2 ) had an 89.8% 18-month retention rate; 83% had eligible follow-up proteomics measurements, and 78% had follow-up proton magnetic resonance spectroscopy. At baseline, 39 candidate proteins were significantly associated with IHF% (false discovery rate <0.05), mostly related to immune function pathways (eg, hydroxyacid oxidase 1). An IHF% prediction based on the DIRECT PLUS by combined model ( R2 = 0.47, root mean square error = 1.05) successfully predicted IHF% ( R2 = 0.53) during testing and was stronger than separately inputting proteins/traditional markers ( R2 = 0.43/0.44). The 18-month lifestyle intervention induced changes in 18 of the 39 candidate proteins, which were significantly associated with IHF% change, with proteins related to metabolism, extracellular matrix remodeling, and immune function pathways. Thrombospondin-2 protein change was higher in the green-MED compared to the MED group, beyond weight and IHF% loss ( p = 0.01). Protein principal component analysis revealed differences in the third principal component time distinct interactions across abnormal/normal IHF% trajectory combinations; p < 0.05 for all).

Conclusions: Our findings suggest novel proteomic signatures that may indicate MRI-assessed IHF state and changes during lifestyle intervention. Specifically, carbonic anhydrase 5A, hydroxyacid oxidase 1, and thrombospondin-2 protein changes are independently associated with IHF% change, and thrombospondin-2 protein change is greater in the green-MED/high polyphenols diet.

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来源期刊
Hepatology
Hepatology 医学-胃肠肝病学
CiteScore
27.50
自引率
3.70%
发文量
609
审稿时长
1 months
期刊介绍: HEPATOLOGY is recognized as the leading publication in the field of liver disease. It features original, peer-reviewed articles covering various aspects of liver structure, function, and disease. The journal's distinguished Editorial Board carefully selects the best articles each month, focusing on topics including immunology, chronic hepatitis, viral hepatitis, cirrhosis, genetic and metabolic liver diseases, liver cancer, and drug metabolism.
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