Genetic Factors and Molecular Mechanisms of Vitamin D and Obesity Relationship

Abstract

Vitamin D (vitD) deficiency is associated with a wide range of chronic diseases and conditions, including obesity, and with an increasing severity of metabolic dysregulation, such as insulin resistance, hyperlipidemia, liver disease, and hypertension, both in children and adults. However, the nature of the association between low vitD status and obesity remains unclear. This fact has motivated the scientific community to conduct genetic association analyses between 25-hydroxyvitamin D (25[OH]D)-related genes and obesity traits. In this line, the variation in the vitD receptor (VDR) gene represents the bulk of the findings. Specifically, polymorphisms in the VDR gene have been associated with obesity traits in some but not all, studies. Thus, results regarding this matter remain inconclusive. Other genes aside from VDR have also been investigated in relation to obesity-related traits. However, again, findings have been inconsistent. In general, results point to the fact that the DBP/GC gene could be an important protein-linking obesity and vitD status. On the other hand, several studies have attempted to determine the molecular mechanism of the relationship between 25(OH)-D levels and obesity. Some of these studies suggest that vitD, due to its fat-soluble characteristic, is retained by the adipose tissue and has the capacity to metabolize 25(OH)-D locally, and this can be altered during obesity. Additionally, vitD is capable of regulating the gene expression related to adipogenesis process, inflammation, oxidative stress, and metabolism in mature adipocytes. Therefore, the aim of the present review was to evaluate the association between obesity and vitD deficiency describing the main molecular mechanism of the relationship and the link with genetic factors. Key Messages: Low serum 25(OH)-D is positively associated with obesity or BMI in adults and children. Circulating vitD concentrations are, at least, partially determined by genetic factors. VitD plays an important role in the adipogenesis process and inflammation status in adipocytes and adipose tissue.

Effect of Vitamin D Supplementation on Cardiometabolic Factors and Inflammatory Status in Adolescents with Obesity Enrolled in a Weight-Loss Program

“…In our study, 70% of adolescents with obesity had baseline 25(OH)-D concentrations lower than 50 nmol/L (equal to 20 ng/mL), which defines deficiency according to the French guidelines [32]. Obesity-related VD insufficiency could be explained by many factors: sun underexposure, inadequate intake of VD-rich foods and beverages, genetic factors [33], sequestration of this fat-soluble vitamin, and its volumetric dilution [34] Our finding that 25(OH)D levels as total and free were increased also in the ONS group after the 3-month lifestyle program suggests a possible release of VD during weight loss in the absence of VD supplementation. Previous studies also reported increased circulating 25(OH)D levels in adults with obesity after adiposity loss through lifestyle interventions without VD supplementation [14].…”

Direct-to-Consumer Nutrigenetics Testing: An Overview

“…Vitamin D is important in a wide range of physiological processes, and its deficit has been related to different chronic diseases and metabolic conditions, including obesity. Nonetheless, encompassing literature studies indicated only a faint association between gene variants acting in vitamin D metabolism and the obese phenotype [33], while the environment seems to play a major role [34][35][36]. The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to the six susceptibility loci harboring genome-wide significant SNPs (recently identified in a large GWAS) is 7.5%, with statistically significant loci explaining 38% of this total [37].…”

Association of VDR gene variant (rs1544410) with type 2 diabetes in a Pakistani cohort

“…There are several reports that these VDR polymorphisms are associated with T2DM and insulin secretion [19][20][21]. In addition, VDR polymorphisms are related to metabolic syndrome, metabolic changes related to obesity [22]. The association of the VDR gene polymorphisms and T2DM in older people living in a community of Santiago de Chile, Chile, were previously established through a case-control study on 138 T2DM patients and 172 control subjects with ages ranging from 60-79 years.…”