Increased Risk of High Body Fat and Altered Lipid Metabolism Associated to Suboptimal Consumption of Vitamin A Is Modulated by Genetic Variants rs5888 (SCARB1), rs1800629 (UCP1) and rs659366 (UCP2).

Sebastià Galmés,Francisca Serra,Andreu Palou

doi:10.3390/nu12092588

Abstract

Obesity is characterized by an excessive body fat percentage (BF%). Animal and cell studies have shown benefits of vitamin A (VA) on BF% and lipid metabolism, but it is still controversial in humans. Furthermore, although some genetic variants may explain heterogeneity in VA plasma levels, their role in VA metabolic response is still scarcely characterized. This study was designed as a combination of an observational study involving 158 male subjects followed by a study with a well-balanced genotype–phenotype protocol, including in the design an ex vivo intervention study performed on isolated peripheral blood mononuclear cells (PBMCs) of the 41 former males. This is a strategy to accurately identify the delivery of Precision Nutrition recommendations to targeted subjects. The study assesses the influence of rs5888 (SCARB1), rs659366 (UCP2), and rs1800629 (UCP1) variants on higher BF% associated with suboptimal VA consumption and underlines the cellular mechanisms involved by analyzing basal and retinoic acid (RA) response on PBMC gene expression. Data show that male carriers with the major allele combinations and following suboptimal-VA diet show higher BF% (adjusted ANOVA test p-value = 0.006). Genotype–BF% interaction is observed on oxidative/inflammatory gene expression and also influences lipid related gene expression in response to RA. Data indicate that under suboptimal consumption of VA, carriers of VA responsive variants and with high-BF% show a gene expression profile consistent with an impaired basal metabolic state. The results show the relevance of consuming VA within the required amounts, its impact on metabolism and energy balance, and consequently, on men’s adiposity with a clear influence of genetic variants SCARB1, UCP2 and UCP1.

Highlights

Obesity is a metabolic disease characterized by excessive fat accumulation which can promote the development of associated disorders, such as diabetes or cardiovascular events, resulting in an increased risk of mortality and considerable public health costs [1]
Thereby, our findings show that three genetic variants, which have not been previously related to fat accumulation, might be predisposed to greater adiposity depending on the amount of vitamin A (VA)
SLC27A2 encodes a key enzyme genes involved in carotenoid absorption could be responsible for high interindividual variability in that bioavailability plays an important role in both lipid biosynthesis and fatty acid degradation [61]. Their its overexpression in rat Peripheral Blood Mononuclear Cells (PBMCs) has three been proposed as an early marker development, Thereby, our findings show that genetic variants, which have of notoverweight been previously related related to inadequate diets

Summary

Introduction

Obesity is a metabolic disease characterized by excessive fat accumulation which can promote the development of associated disorders, such as diabetes or cardiovascular events, resulting in an increased risk of mortality and considerable public health costs [1]. Poor consumption of vitamin A (VA) has been widely related to vision problems [3] and immune system alterations [4], and with a higher prevalence of obesity [5,6] and fat accumulation [7,8]. The main active form of VA is RA which has the capacity to influence the expression of key genes related to lipid and energy homeostasis in mammals [11,12], actively participating in the modulation of adipocyte differentiation, lipogenesis/lipolysis, thermogenesis, and fat oxidation [11,12,13]. The main core of studies on supplementation with BC have been based on the assessment of BC antioxidant action [15], while studies aimed at inducing weight loss or body fat reduction using carotenoid supplementation are still scarce

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