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)

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.

Expressions of mRNA and encoded proteins of mitochondrial uncoupling protein genes (UCP1, UCP2, and UCP3) in epicardial and mediastinal adipose tissue and associations with coronary artery disease

“…Finally, the CAD process is intricate and involves a complex interaction of genes, behavior, and environment, where the role of diet and nutritional deficiency states can interact. For example, vitamin A depletion is known to have an impact on metabolism and energy balance and, consequently, on male adiposity, exerting an evident influence on the genetic variants SCARB1, UCP2 , and UCP1 , although more studies are required for a complete understanding of these mechanisms ( 42 ).…”

Association of Serum Retinol Concentrations With Metabolic Syndrome Components in Iranian Children and Adolescents: The CASPIAN-V Study

“…Many possible reasons may be accounted for the paradoxical findings on the association between serum retinol concentration and obesity or metabolic health during childhood or adolescence. First, it seems that circulating vitamin A level and its role in vitamin A metabolic response is influenced by some genetic variations (44,60). For instance, genetic variants in genes such as SCARB1, UCP2, and UCP1 have been shown to modulate the effect of vitamin A intake on metabolism and energy balance and, consequently, adiposity measure, i.e., insufficient vitamin A intake is associated with a greater risk of body fat accumulation in genetically predisposed individuals (44).…”

Dietary Sources, Sex, and rs5888 (SCARB1) as Modulators of Vitamin A’s Effect on Cardiometabolic Health

“…The total number of participants in the Ob-IB study was 490. All of them met the inclusion criteria (mainly, ≥18 years old who read and signed the informed consent) and did not report any of the exclusion criteria to participate in the project (lactating, pregnant, and/or carriers of contagious diseases; see [ 33 ] for details). In addition, subjects who reported taking supplements that may affect the nutritional status of VA were not included in the analysis.…”

“…RNA quantification was carried out with the spectrophotometer Nanodrop 1000 (Thermo-Fisher Scientific, Waltham, MA, USA). Gene expression was performed by real-time PCR (qPCR) using Power SYBR Green Master Mix (Applied Biosystems, Madrid, Spain), as described in more detail elsewhere [ 33 ]. Primers were designed by researchers involved in the OptiDiet-15 study and were purchased from Sigma Genosys (Sigma-Aldrich Química SA, Madrid, Spain).…”