Metabolites mediate immune cells to participate in the occurrence of non-alcoholic fatty liver disease:a multivariate Mendelian randomization analysis
DAI Hongyuan
QIAN Zhenwei
LU Yinying
HAN Juqiang
Abstract：Objective To investigate the independent causal relationship between immune cells and metabolites in the pathogenesis of non-alcoholic fatty liver disease(NAFLD),and to pay attention to the mediating role of metabolites in NAFLD caused by immune cell changes,so as to lay the foundation for further research on the pathogenesis of NAFLD.Methods The immune cells and metabolites associated with NAFLD were screened by Mendelian randomization(MR)analysis.Then,MR was performed separately to obtain the corresponding beta values.Finally,the direct effect,mediation effect and effect ratio were calculated.Results Our study obtained 4 types of immune cells and 22 types of metabolites related to the pathogenesis of NAFLD.The immune cell"Naive CD4+％CD4+"predicted based on single nucleotide polymorphisms was associated with an increased risk of NAFLD,and 8.96％of the risk was mediated by levels of"Pregnenetriol disulfate".Conclusion This study identified a close connection between immune cells and metabolites and NAFLD through MR analysis,in which the increase of"Naive CD4+％CD4+"may promote the development of NAFLD through increased"Pregnenetriol disulfate"levels.
Keywords：non-alcoholic fatty liver diseasenon-alcoholic steatohepatitisMendelian randomizationmetabolitesCD4+T cellsNaive CD4+T cells
Publication Date：2026-06-30
Online Publishing Date：2026-08-26(First online date of this platform, not the publication date of the document)
Pages：7( 812-818 )