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ORIGINAL RESEARCH article

Front. Endocrinol.
Sec. Systems Endocrinology
Volume 15 - 2024 | doi: 10.3389/fendo.2024.1436827
This article is part of the Research Topic Genetics and multi-omics approach in metabolic liver disorders View all 5 articles

Role of plasma metabolome in mediating the effect of plasma lipidome on NAFLD: a Mendelian randomization study

Provisionally accepted
Zhuyuan Zheng Zhuyuan Zheng 1Shaojie Yang Shaojie Yang 1Wanlin Dai Wanlin Dai 2Yang Sun Yang Sun 1Jingnan Wang Jingnan Wang 1Xiaolin Zhang Xiaolin Zhang 1Yiming Zheng Yiming Zheng 1Jing Kong Jing Kong 3*
  • 1 Shengjing Hospital of China Medical University, Shengyang, China
  • 2 China Medical University, Shenyang, Liaoning Province, China
  • 3 Sheng Jing Hospital Affiliated, China Medical University, Shenyang, China

The final, formatted version of the article will be published soon.

    Exploring the causal connection among the plasma lipidome, nonalcoholic fatty liver disease (NAFLD), and potential metabolome mediators through Mendelian randomization (MR).We obtained summary statistics for 179 plasma lipidome traits (N = 7,174), 1,400 plasma metabolome traits (N = 8,299), and 1 NAFLD trait from publicly available genome-wide association studies. A two-sample MR analysis was conducted to infer causality. Additionally, multiple sensitivity analyses were conducted to assess the heterogeneity, horizontal pleiotropy, and robustness performed to verify the reliability of the MR findings. MetaboAnalyst 6.0 was used for the pathway analysis of the identified lipids and metabolites. Furthermore, we used mediation analysis to assess whether the effect of plasma lipidome on NAFLD was mediated by plasma metabolome.MR analysis identified higher genetically predicted a causal relationship between plasma lipidomes and NAFLD. No compelling proof was found that genetically 2 predicted NAFLD influenced the risk of the 5 plasma lipidomes mentioned earlier.Based on established causal relationships between lipids and metabolites, we identified that 11 8 metabolic pathways are closely associated with NAFLD. Our mediation analysis revealed 6 mediation relationships, indicating the causal pathway from plasma lipids to NAFLD mediated by 45 specific metabolites. No potential pleiotropy was found in the sensitivity analysis.In summary, our study identified causal relationships between plasma lipidomes, plasma metabolomes and NAFLD. Certainly, the impact of plasma lipidomes on NAFLD is not limited to plasma metabolomes, indicating a need for further investigating into other possible mediators. These identified factors may become new biomarkers of the NAFLD contributing to its prevention, diagnosis, and treatment.

    Keywords: Mendelian Randomization (MR), Nonalcoholic fatty liver disease (NAFLD), Plasma lipidome, Plasma Metabolome, mediation analysis;

    Received: 22 May 2024; Accepted: 23 Dec 2024.

    Copyright: © 2024 Zheng, Yang, Dai, Sun, Wang, Zhang, Zheng and Kong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Jing Kong, Sheng Jing Hospital Affiliated, China Medical University, Shenyang, China

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