Identification of Genetic Polymorphisms Associated with Interindividual Variability of Vitamin A Concentration in Adipose Tissue of Healthy Male Adults

IF 3.7 3区医学 Q2 NUTRITION & DIETETICS Journal of Nutrition Pub Date : 2024-12-01 DOI:10.1016/j.tjnut.2024.10.035

Mark Pretzel Zumaraga , Charles Desmarchelier , Beatrice Gleize , Marion Nowicki , Djaffar Ould-Ali , Jean-François Landrier , Patrick Borel

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Abstract

Background

Adipose tissue vitamin A (VA), that is, mainly retinol (RET) and its esters, comes from preformed VA and proVA carotenoids present in our food. Adipose tissue VA acts as hormonal cue maintaining essential aspects of adipocyte biology, which includes fat mobilization and catabolism, energy balance, and glucose homeostasis, and it is thus of particular interest to study its determinants, including genetic ones.

Objectives

This study aimed to identify genetic variations associated with adipose tissue VA concentration.

Methods

Forty-two healthy male adults received, in a randomized crossover design, 3 test meals. Periumbilical adipose tissue samples were collected on 6 occasions, that is, at fast and 8 h after consumption of each meal. RET concentration was measured in both plasma and the adipose tissue following saponification. Participants were genotyped using whole-genome microarrays. A total of 1305 single nucleotide polymorphism (SNPs) in or near 27 candidate genes were included for univariate analysis. Partial least squares (PLS) regression was carried out to find the best combination of SNPs associated with the interindividual variability in adipose tissue RET concentration.

Results

Adipose tissue RET concentration was not associated with plasma RET concentrations (r = –0.184, P = 0.28). Interindividual variability of adipose tissue RET concentration was high (coefficient of variation = 62%). Twenty-nine SNPs were significantly (P < 0.05) associated with adipose tissue RET concentration and a PLS regression model identified 16 SNPs as explanatory variables of this concentration. The SNPs were in or near peroxisome proliferator activated receptor gamma, retinoid X receptor alpha, signaling receptor and transporter of retinol, cluster of differentiation 36, free fatty acid receptor 4, aldehyde dehydrogenase 1 family member A1, monoglyceride lipase, diacylglycerol O-acyltransferase 2, and polycystic kidney disease 1-like 2.

Conclusions

A combination of 16 SNPs has been associated with the interindividual of adipose tissue VA concentration in humans.

This trial was registered at clinicaltrials.gov as NCT02100774.

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鉴定与健康男性成年人脂肪组织中维生素 A 浓度个体间差异相关的基因多态性。

背景：脂肪组织维生素 A (VA)，即主要是视黄醇 (RET) 及其酯类，来自食物中预先形成的 VA 和原 VA 类胡萝卜素。脂肪组织 VA 是维持脂肪细胞生物学重要方面（包括脂肪动员和分解代谢、能量平衡和葡萄糖稳态）的激素线索，因此研究其决定因素（包括遗传因素）特别有意义。因此，本研究旨在确定与脂肪组织 VA 浓度相关的遗传变异：方法：42 名健康男性成年人接受了 3 次随机交叉设计的试验餐。脐周脂肪组织样本共采集了 6 次，分别在空腹和进餐后 8 小时采集。皂化后测量血浆和脂肪组织中的 RET 浓度。使用全基因组芯片对参与者进行了基因分型。27 个候选基因中或其附近共有 1305 个 SNPs 被纳入单变量分析。进行了偏最小二乘回归（PLS），以找出与脂肪组织 RET 浓度个体间差异相关的 SNPs 最佳组合：结果：脂肪组织RET浓度与血浆RET浓度无关（r=-0.184，p=0.28）。脂肪组织 RET 浓度的个体间变异性很高（CV=62%）。29 个 SNPs 具有显著性差异（p 结论：16 个 SNPs 的组合已被证实具有显著性差异：16个SNPs的组合与人类脂肪组织VA浓度的个体间差异有关：临床试验注册：ClinicalTrials.gov 注册号 NCT02100774。

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

Journal of Nutrition 医学-营养学

CiteScore

7.60

自引率

4.80%

发文量

260

审稿时长

39 days

期刊介绍： The Journal of Nutrition (JN/J Nutr) publishes peer-reviewed original research papers covering all aspects of experimental nutrition in humans and other animal species; special articles such as reviews and biographies of prominent nutrition scientists; and issues, opinions, and commentaries on controversial issues in nutrition. Supplements are frequently published to provide extended discussion of topics of special interest.