Genetic Factors and Molecular Mechanisms of Vitamin D and Obesity Relationship

This is the peer-reviewed but unedited manuscript version of the following article: [Ann Nutr Metab 2018;73:89–99 (DOI: 10.1159/000490669)]. The final, published version is available at http://www.karger.com/?doi=[10.1159/000490669].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 factorsThis work was supported by Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica (I+D+I), Instituto de Salud Carlos III-Fondo de Investigación Sanitaria (PI1600871 and IFI17/00048) and Fondo Europeo De Desarrollo Regional (FEDER)