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血脂谱与肌肉萎缩之间的因果关系:一项双向孟德尔随机化研究。

Causal relationship between lipid profile and muscle atrophy: A bi-directional Mendelian randomization study.

作者信息

Chen Kun, Gao Peng, Fang Xiaoxiang, Tang Kexing, Ouyang Pan, Li Zongchao, Li Liangjun, Deng Zhenhan

机构信息

Department of Orthopaedics, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, Hunan, China.

Department of Orthopaedic Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

出版信息

Animal Model Exp Med. 2025 Jan;8(1):154-161. doi: 10.1002/ame2.12373. Epub 2023 Dec 28.

Abstract

BACKGROUND

The aim of this study was to analyze the bi-directional causal relationship between lipid profile and characteristics related to muscle atrophy by using a bi-directional Mendelian randomization (MR) analysis.

METHODS

The appendicular lean mass (ALM), whole body fat-free mass (WBFFM) and trunk fat-free mass (TFFM) were used as genome-wide association study (GWAS) data for evaluating muscle mass; the usual walking pace (UWP) and low grip strength (LGS) were used as GWAS data for evaluating muscle strength; and the triglycerides (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL), low density lipoprotein cholesterol (LDL), apolipoprotein A-1 (Apo A-1), and apolipoprotein B (Apo B) were used as GWAS data for evaluating lipid profile. For specific investigations, we mainly employed inverse variance weighting for causal estimation and MR-Egger for pleiotropy analysis.

RESULTS

MR results showed that the lipid profile predicted by genetic variants was negatively correlated with muscle mass, positively correlated with UWP, and was not causally correlated with LGS. On the other hand, the muscle mass predicted by genetic variants was negatively correlated with lipid profile, the UWP predicted by genetic variants was mainly positively correlated with lipid profile, while the LGS predicted by genetic variants had no relevant causal relationship with lipid profile.

CONCLUSIONS

Findings of this MR analysis suggest that hyperlipidemia may affect muscle mass and lead to muscle atrophy, but has no significant effect on muscle strength. On the other hand, increased muscle mass may reduce the incidence of dyslipidemia.

摘要

背景

本研究旨在通过双向孟德尔随机化(MR)分析,分析血脂谱与肌肉萎缩相关特征之间的双向因果关系。

方法

将四肢瘦体重(ALM)、全身去脂体重(WBFFM)和躯干去脂体重(TFFM)用作全基因组关联研究(GWAS)数据以评估肌肉质量;将平常步行速度(UWP)和低握力(LGS)用作GWAS数据以评估肌肉力量;将甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL)、低密度脂蛋白胆固醇(LDL)、载脂蛋白A-1(Apo A-1)和载脂蛋白B(Apo B)用作GWAS数据以评估血脂谱。对于具体研究,我们主要采用逆方差加权进行因果估计,并采用MR-Egger进行多效性分析。

结果

MR结果显示,由遗传变异预测的血脂谱与肌肉质量呈负相关,与UWP呈正相关,与LGS无因果关系。另一方面,由遗传变异预测的肌肉质量与血脂谱呈负相关,由遗传变异预测的UWP主要与血脂谱呈正相关,而由遗传变异预测的LGS与血脂谱无相关因果关系。

结论

该MR分析结果表明,高脂血症可能影响肌肉质量并导致肌肉萎缩,但对肌肉力量无显著影响。另一方面,增加肌肉质量可能会降低血脂异常的发生率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f20c/11798746/51b55a55d743/AME2-8-154-g002.jpg

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