Unveiling the endocrine connections of NAFLD: evidence from a comprehensive mendelian randomization study.

IF 3.2 4区医学 Q2 ENGINEERING, BIOMEDICAL

Biomedical Engineering Letters Pub Date : 2024-12-06 eCollection Date: 2025-01-01 DOI:10.1007/s13534-024-00442-8

Fan Li, Mingjun Wu, Fenfen Wang, Linfei Luo, Zhengqiang Wu, Zixiang Huang, Zhili Wen

{"title":"Unveiling the endocrine connections of NAFLD: evidence from a comprehensive mendelian randomization study.","authors":"Fan Li, Mingjun Wu, Fenfen Wang, Linfei Luo, Zhengqiang Wu, Zixiang Huang, Zhili Wen","doi":"10.1007/s13534-024-00442-8","DOIUrl":null,"url":null,"abstract":"Background: NAFLD is gaining recognition as a complex, multifactorial condition with suspected associations with endocrine disorders. This investigation employed MR analysis to explore the potential causality linking NAFLD to a spectrum of endocrine diseases, encompassing T1D, T2D, obesity, graves' disease, and acromegaly.Methods: Our methodology leveraged a stringent IV selection process, adhering to the STROBE-MR guidelines. The MR analysis was conducted utilizing three distinct methods: IVW, WM, and MR-Egger. The IVW method was prioritized as the primary analytical approach. We conducted MR analyses to analyze the causal relationship between NAFLD and metabolic disorders. We also examined 1400 metabolites implicated in NAFLD. Metabolic pathway analysis was performed using the MetaboAnalyst database.Results: The findings indicated that T2D (OR = 1.211, 95%CI: 0.836-1.585) and obesity (OR = 1.245, 95%CI: 0.816-1.674) are associated with an increased risk of NAFLD development. Further exploration into the the 1400 metabolites revealed that cys-gly and diacetylornithine are predictive of NAFLD, T2D, and obesity, whereas isovalerylcarnitine exhibited an inverse association, potentially inhibiting disease development. Metabolic pathways involving alanine, aspartate, and glutamate metabolism were identified as pivotal regulators in the pathophysiology of NAFLD, T2D, and obesity.Conclusion: The present study generated innovative viewpoints on the etiology of NAFLD. Our findings underscore the significant role of T2D and obesity in NAFLD pathogenesis through metabolic pathways, presenting opportunities for targeted therapeutic strategies and warranting further investigation.Supplementary information: The online version contains supplementary material available at 10.1007/s13534-024-00442-8.","PeriodicalId":46898,"journal":{"name":"Biomedical Engineering Letters","volume":"15 1","pages":"239-248"},"PeriodicalIF":3.2000,"publicationDate":"2024-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704114/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biomedical Engineering Letters","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1007/s13534-024-00442-8","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}

引用次数: 0

Abstract

Background: NAFLD is gaining recognition as a complex, multifactorial condition with suspected associations with endocrine disorders. This investigation employed MR analysis to explore the potential causality linking NAFLD to a spectrum of endocrine diseases, encompassing T1D, T2D, obesity, graves' disease, and acromegaly.

Methods: Our methodology leveraged a stringent IV selection process, adhering to the STROBE-MR guidelines. The MR analysis was conducted utilizing three distinct methods: IVW, WM, and MR-Egger. The IVW method was prioritized as the primary analytical approach. We conducted MR analyses to analyze the causal relationship between NAFLD and metabolic disorders. We also examined 1400 metabolites implicated in NAFLD. Metabolic pathway analysis was performed using the MetaboAnalyst database.

Results: The findings indicated that T2D (OR = 1.211, 95%CI: 0.836-1.585) and obesity (OR = 1.245, 95%CI: 0.816-1.674) are associated with an increased risk of NAFLD development. Further exploration into the the 1400 metabolites revealed that cys-gly and diacetylornithine are predictive of NAFLD, T2D, and obesity, whereas isovalerylcarnitine exhibited an inverse association, potentially inhibiting disease development. Metabolic pathways involving alanine, aspartate, and glutamate metabolism were identified as pivotal regulators in the pathophysiology of NAFLD, T2D, and obesity.

Conclusion: The present study generated innovative viewpoints on the etiology of NAFLD. Our findings underscore the significant role of T2D and obesity in NAFLD pathogenesis through metabolic pathways, presenting opportunities for targeted therapeutic strategies and warranting further investigation.

Supplementary information: The online version contains supplementary material available at 10.1007/s13534-024-00442-8.

查看原文本刊更多论文

揭示NAFLD的内分泌联系：来自全面孟德尔随机研究的证据。

背景：NAFLD被认为是一种复杂的、多因素的疾病，可能与内分泌紊乱有关。本研究采用磁共振分析探讨NAFLD与一系列内分泌疾病的潜在因果关系，包括T1D、T2D、肥胖、graves病和肢端肥大症。方法：我们的方法利用了严格的IV选择过程，坚持STROBE-MR指南。磁共振分析采用三种不同的方法：IVW、WM和MR- egger。IVW法被优先考虑为主要分析方法。我们通过MR分析来分析NAFLD与代谢紊乱之间的因果关系。我们还检查了1400种与NAFLD有关的代谢物。使用MetaboAnalyst数据库进行代谢途径分析。结果：研究结果表明，T2D （OR = 1.211, 95%CI: 0.836-1.585）和肥胖（OR = 1.245, 95%CI: 0.816-1.674）与NAFLD发生风险增加相关。对1400种代谢物的进一步研究表明，cyys -gly和二乙酰鸟氨酸可预测NAFLD、T2D和肥胖，而异戊基肉碱则表现出负相关，可能抑制疾病的发展。包括丙氨酸、天冬氨酸和谷氨酸代谢在内的代谢途径被认为是NAFLD、T2D和肥胖病理生理中的关键调节因子。结论：本研究对NAFLD的病因有了新的认识。我们的发现强调了T2D和肥胖通过代谢途径在NAFLD发病机制中的重要作用，为有针对性的治疗策略提供了机会，并值得进一步研究。补充信息：在线版本包含补充资料，提供地址：10.1007/s13534-024-00442-8。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Biomedical Engineering Letters ENGINEERING, BIOMEDICAL-

CiteScore

6.80

自引率

0.00%

发文量

期刊介绍： Biomedical Engineering Letters (BMEL) aims to present the innovative experimental science and technological development in the biomedical field as well as clinical application of new development. The article must contain original biomedical engineering content, defined as development, theoretical analysis, and evaluation/validation of a new technique. BMEL publishes the following types of papers: original articles, review articles, editorials, and letters to the editor. All the papers are reviewed in single-blind fashion.