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Accepted manuscript

The protective effect of higher serum triacylglycerol (51:4) levels against Parkinson’s disease

Published online by Cambridge University Press:  11 November 2024

Yajun Jing
Affiliation:
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
Jinye Su
Affiliation:
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
Honglin Zhu
Affiliation:
Faculty of Life Sciences and Medicine, King’s College London, London, UK
Yiming Chen
Affiliation:
Department of Medical Laboratory, College of Medical Technology and Engineering, Fujian Medical University, Fuzhou, Taijiang District, Fuzhou, Fujian, China, 350004
Surmai Shukla
Affiliation:
Department of immunology, Northwestern University, Evanston, Illinois, the United States of America.
Lianghong Yu*
Affiliation:
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Department of Neurosurgery, Binhai Branch of National Regional Medical Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350209, Fujian, China.
Dezhi Kang
Affiliation:
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Department of Neurosurgery, Binhai Branch of National Regional Medical Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350209, Fujian, China. Fujian Provincial Institutes of Brain Disorders and Brain Sciences, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Institute of Neurology, First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China.
Dengliang Wang
Affiliation:
Department of Neurosurgery, Neurosurgery Research Institute, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350005, Fujian, China. Department of Neurosurgery, Binhai Branch of National Regional Medical Center, The First Affiliated Hospital, Fujian Medical University, Fuzhou 350209, Fujian, China.
*
Corresponding authors: Dengliang Wang, e-mail: [email protected]; Lianghong Yu, e-mail: [email protected]; Dezhi Kang, e-mail: [email protected]
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Abstract

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Emerging evidence has shown a strong correlation between serum triacylglycerol (TAG) levels, the inflammatory response, and Parkinson’s disease (PD) onset. However, the causal relationship between TAG levels and PD has not been well-established. We aimed to investigate the relationship between serum TAG levels and risk of PD and explore the potential mediating role of circulating immune cells and inflammatory proteins. We utilised genotype data from the GeneRISK cohort, and summary data from genome wide association studies investigating PD, circulating immune cells, inflammatory proteins, and plasma lipidomes. Using Mendelian randomization (MR) and multivariate MR (MVMR) analysis, we further adjusted for phosphatidylcholine (17:0_18:1) and triacylglycerol (58:7). Our results suggested a robust causal link between higher serum TAG (51:4) levels and a decreased risk of PD, with one standard deviation genetically instrumented higher serum TAG (51:4) level leading to a 21 percent [95% CI, 0.66 – 0.96] reduction in the risk of PD (p = 0.015). Additionally, the results of the mediation analysis suggested a possible role for mediation through circulating immune cells (including IgD-CD38-B cells and resting CD4 regulatory T cells), but not circulating inflammatory proteins, in the causal relationship between the plasma lipidomes and PD. Our study confirms a causal relationship between higher serum TAG (51:4) levels and a lower risk of PD and clarifies a possible role for mediation through circulating immune cells, but not inflammatory proteins. These findings indicate that serum triacylglycerol (51:4) regulates immunity to effectively lower the risk of PD.

Type
Research Article
Copyright
© The Authors 2024

Footnotes

First author: Yajun Jing, e-mail: [email protected].