The role of circulating polyunsaturated fatty acids in mediating the effect of BMI on leukocyte telomere length: analysis using Mendelian randomization

polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte tel...

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Published in:Nutrition & metabolism 2024-12, Vol.21 (1), p.104-14
Main Authors: Tan, Li, Zhong, Meng-Mei, Zhao, Ya-Qiong, Feng, Yao, Ye, Qin, Hu, Jing, Ou-Yang, Ze-Yue, Chen, Ning-Xin, Su, Xiao-Lin, Zhang, Qian, Liu, Qiong, Yuan, Hui, Wang, Min-Yuan, Feng, Yun-Zhi, Guo, Yue
Format: Article
Language:English
Subjects:
Aging
Analysis
BMI
Body mass index
Circulating polyunsaturated fatty acids
Composition
Fatty acids
Genetic aspects
Genetic association
Genomics
Health aspects
Leukocyte telomere length
Measurement
Mediation
Mendelian randomization
Nutritional aspects
Omega-3 fatty acids
Telomeres
Unsaturated fatty acids
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Summary:polyunsaturated fatty acids (PUFAs) are a category of fatty acids that contain omega-3 and omega-6 fatty acids, which constitute a substantial portion of the Western diet and are vital for maintaining human wellness. The extent to which circulating PUFAs influence the effects of BMI on leukocyte telomere length (LTL) is unknown. Additionally, the impact of circulating PUFA on LTL remains controversial in observational studies. Using publicly accessible datasets, a genome-wide association study (GWAS) was carried out to determine genetic association estimates for BMI, circulating PUFAs, and LTL. The circulating PUFAs considered were omega-3 PUFAs (i.e., docosahexaenoic acid (DHA) and total omega-3 PUFAs) and omega-6 PUFAs (i.e., linoleic acid (LA) and total omega-6 PUFAs). Two-sample Mendelian randomization (MR) was used to investigate the causal relationships between BMI and PUFA with LTL. Additionally, we examined whether certain PUFA mediate the impact of BMI on LTL. None of the evidence supported a causal effect of genetically predicted DHA and total omega-3 PUFA on LTL (DHA: β = 0.001, 95% CI: -0.023 to 0.026, p = 0.926; total omega-3 PUFA: β = 0.008, 95% CI: -0.013 to 0.029, p = 0.466). After conducting sensitivity analyses to account for various models of horizontal pleiotropy, the causal association between higher levels of LA and longer LTL persisted (β = 0.034, 95% CI 0.016 to 0.052, p 
ISSN:1743-7075
1743-7075
DOI:10.1186/s12986-024-00882-0