Li Fan, Wu Mingjun, Wang Fenfen, Luo Linfei, Wu Zhengqiang, Huang Zixiang, Wen Zhili
Department of Gastroenterology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, 330006 China.
Nanchang Hongdu Hospital of Traditional Chinese Medicine, Nanchang, China.
Biomed Eng Lett. 2024 Dec 6;15(1):239-248. doi: 10.1007/s13534-024-00442-8. eCollection 2025 Jan.
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.
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.
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.
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.
The online version contains supplementary material available at 10.1007/s13534-024-00442-8.
非酒精性脂肪性肝病（NAFLD）正逐渐被视为一种复杂的多因素疾病，疑似与内分泌紊乱有关。本研究采用孟德尔随机化（MR）分析，以探讨NAFLD与一系列内分泌疾病（包括1型糖尿病、2型糖尿病、肥胖症、格雷夫斯病和肢端肥大症）之间的潜在因果关系。
我们的方法采用了严格的IV选择过程，遵循STROBE-MR指南。MR分析使用了三种不同的方法：逆方差加权法（IVW）、加权中位数法（WM）和MR-Egger回归法。IVW方法被优先作为主要分析方法。我们进行了MR分析，以分析NAFLD与代谢紊乱之间的因果关系。我们还研究了1400种与NAFLD相关的代谢物。使用MetaboAnalyst数据库进行代谢途径分析。
研究结果表明，2型糖尿病（OR = 1.211，95%CI：0.836 - 1.585）和肥胖症（OR = 1.245，95%CI：0.816 - 1.674）与NAFLD发生风险增加有关。对这1400种代谢物的进一步研究表明，胱氨酸 - 甘氨酸和二乙酰鸟氨酸可预测NAFLD、2型糖尿病和肥胖症，而异戊酰肉碱则呈现负相关，可能抑制疾病发展。涉及丙氨酸、天冬氨酸和谷氨酸代谢的代谢途径被确定为NAFLD、2型糖尿病和肥胖症病理生理学中的关键调节因子。
本研究对NAFLD的病因学提出了新观点。我们的研究结果强调了2型糖尿病和肥胖症在NAFLD发病机制中通过代谢途径的重要作用，为靶向治疗策略提供了机会，值得进一步研究。
在线版本包含可在10.1007/s13534-024-00442-8获取的补充材料。
