中国科学院遗传与发育生物学研究所税光厚等研究人员合作发现，MASLD纤维化过渡的非侵入性脂质组揭示，脂蛋白硫酸脑苷脂在肝脏免疫调节中的作用。这一研究成果于2024年11月4日在线发表在国际学术期刊《细胞—代谢》上。

研究人员对来自PERSONS队列的血清样本，进行了定量脂质组学和甾醇组学分析，并通过活检基础的肝脏病理学评估对其进行研究。研究人员使用定量组学数据和临床变量训练了一个lasso回归模型，得出了一个脂质和临床指标的组合，能够区分轻度纤维化（>F1，n=324）与非纤维化（F0，n=195），其受试者工作特征曲线下面积（AUROC）为0.775（95%置信区间[CI]：0.735-0.816）。

循环中的硫酸脑苷脂（SL），是与代谢功能障碍相关脂肪性肝病（MASLD）纤维化发病机制显著相关的核心脂质。脂质组学分析表明，MASLD纤维化中循环SLs在高密度脂蛋白（HDL）与低密度脂蛋白（LDL）之间重新分布。研究人员进一步验证了，患者的LDL中减少的SL含量触发了较小的II型自然杀伤T细胞激活，相较于对照组LDL。这些结果表明，肝脏与全身免疫的相互作用通过脂蛋白代谢介导，构成了MASLD早期阶段纤维化进展的基础。

据悉，在MASLD中，迫切需要一种非侵入性组合来区分轻度纤维化与非纤维化。

附：英文原文

Title: Non-invasive lipid panel of MASLD fibrosis transition underscores the role of lipoprotein sulfatides in hepatic immunomodulation

Author: Sin Man Lam, Zehua Wang, Jin-Wen Song, Yue Shi, Wen-Yue Liu, Lin-Yu Wan, Kaibo Duan, Gek Huey Chua, Yingjuan Zhou, Guibin Wang, Xiahe Huang, Yingchun Wang, Fu-Sheng Wang, Ming-Hua Zheng, Guanghou Shui

Issue&Volume: 2024-11-04

Abstract: There exists a pressing need for a non-invasive panel that differentiates mild fibrosis from non-fibrosis in metabolic dysfunction-associated steatotic liver disease (MASLD). In this work, we applied quantitative lipidomics and sterolomics on sera from the PERSONS cohort with biopsy-based histological assessment of liver pathology. We trained a lasso regression model using quantitative omics data and clinical variables, deriving a combinatorial panel of lipids and clinical indices that differentiates mild fibrosis (>F1, n = 324) from non-fibrosis (F0, n = 195), with an area under receiver operating characteristic curve (AUROC) at 0.775 (95% confidence interval [CI]: 0.735–0.816). Circulating sulfatides (SLs) emerged as central lipids distinctly associated with fibrosis pathogenesis in MASLD. Lipidomics analysis of lipoprotein fractions revealed a redistribution of circulating SLs from high-density lipoproteins (HDLs) onto low-density lipoproteins (LDLs) in MASLD fibrosis. We further verified that patient LDLs with reduced SL content triggered a smaller activation of type II natural killer T lymphocytes, compared with control LDLs. Our results suggest that hepatic crosstalk with systemic immunity mediated by lipoprotein metabolism underlies fibrosis progression at early-stage MASLD.

DOI: 10.1016/j.cmet.2024.09.009

Source: https://www.cell.com/cell-metabolism/abstract/S1550-4131(24)00373-5