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

IF 3.9 2区医学 Q2 NUTRITION & DIETETICS

Nutrition & Metabolism Pub Date : 2024-12-05 DOI:10.1186/s12986-024-00882-0

Li Tan, Meng-Mei Zhong, Ya-Qiong Zhao, Yao Feng, Qin Ye, Jing Hu, Ze-Yue Ou-Yang, Ning-Xin Chen, Xiao-Lin Su, Qian Zhang, Qiong Liu, Hui Yuan, Min-Yuan Wang, Yun-Zhi Feng, Yue Guo

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引用次数: 0

Abstract

Background: 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.

Methods: 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.

Results: 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 < 0.001). Adjusting for LA in genetics reduced the effect of BMI on LTL from β = -0.039 (95% CI: -0.058 to -0.020, p < 0.001) to -0.034 (95% CI: -0.054 to -0.014, p < 0.001).

Conclusions: This MR study indicates that an increase in genetically predicted circulating LA levels is associated with longer LTL. Additionally, it appears that circulating LA levels play a role in mediating some of the impact that BMI has on LTL.

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循环多不饱和脂肪酸在介导BMI对白细胞端粒长度的影响中的作用：使用孟德尔随机化分析。

背景：多不饱和脂肪酸（PUFAs）是一类含有omega-3和omega-6脂肪酸的脂肪酸，它们构成了西方饮食的很大一部分，对维持人体健康至关重要。循环PUFAs影响BMI对白细胞端粒长度（LTL）的影响程度尚不清楚。此外，在观察性研究中，循环PUFA对LTL的影响仍存在争议。方法：利用可公开访问的数据集，开展了一项全基因组关联研究（GWAS），以确定BMI、循环PUFAs和LTL的遗传关联估计。考虑的循环PUFAs是omega-3 PUFAs（即二十二碳六烯酸（DHA）和总omega-3 PUFAs）和omega-6 PUFAs（即亚油酸（LA）和总omega-6 PUFAs）。采用双样本孟德尔随机化（MR）研究BMI、PUFA与LTL之间的因果关系。此外，我们研究了某些PUFA是否介导BMI对LTL的影响。结果：没有证据支持遗传预测的DHA和总omega-3 PUFA对LTL的因果影响(DHA: β = 0.001, 95% CI: -0.023 ~ 0.026, p = 0.926；总omega-3 PUFA: β = 0.008, 95% CI: -0.013至0.029,p = 0.466)。在对各种水平多效性模型进行敏感性分析后，高水平的LA与较长的LTL之间的因果关系仍然存在（β = 0.034, 95% CI 0.016至0.052,p）。结论：这项MR研究表明，遗传预测的循环LA水平的增加与较长的LTL有关。此外，循环LA水平似乎在BMI对LTL的一些影响中起中介作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nutrition & Metabolism 医学-营养学

CiteScore

8.40

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition & Metabolism publishes studies with a clear focus on nutrition and metabolism with applications ranging from nutrition needs, exercise physiology, clinical and population studies, as well as the underlying mechanisms in these aspects. The areas of interest for Nutrition & Metabolism encompass studies in molecular nutrition in the context of obesity, diabetes, lipedemias, metabolic syndrome and exercise physiology. Manuscripts related to molecular, cellular and human metabolism, nutrient sensing and nutrient–gene interactions are also in interest, as are submissions that have employed new and innovative strategies like metabolomics/lipidomics or other omic-based biomarkers to predict nutritional status and metabolic diseases. Key areas we wish to encourage submissions from include: -how diet and specific nutrients interact with genes, proteins or metabolites to influence metabolic phenotypes and disease outcomes; -the role of epigenetic factors and the microbiome in the pathogenesis of metabolic diseases and their influence on metabolic responses to diet and food components; -how diet and other environmental factors affect epigenetics and microbiota; the extent to which genetic and nongenetic factors modify personal metabolic responses to diet and food compositions and the mechanisms involved; -how specific biologic networks and nutrient sensing mechanisms attribute to metabolic variability.