Estudio nutrigenético de la obesidad en la población de Mallorca

Resumen

Introduction Obesity is a major health problem that also involves high economic cost due to its close relationship with increased risk of suffering other metabolic disorders, such as type 2 diabetes, hypertension and, cardiovascular problems. Epidemiological studies have identified inadequate diets, physical inactivity and genetic factors, as some of the main causes of the obesity pandemic. Despite the location of the Mallorca in the environment of the Mediterranean diet, its inhabitants have a high rate of obesity and mortality associated with cardiovascular problems in comparison with other areas of Spain. Furthermore, underlying causes are not entirely understood. On the other hand, evidence exist about the effect of the consumption of specific nutrients in modifying the genetic risk associated with the presence of genetic variants; which is known as gene-nutrient interaction and may impact on the phenotype. In this context, the aim of the study was to analyse whether the existence of specific genetic factors in the population of Mallorca, together with relatively inadequate dietary and lifestyle habits -as well as their interaction- could be relevant elements in the prevalence of obesity and cardiovascular risk. To accomplish the aim of this Doctoral Thesis, recruitment and characterization at anthropometric, dietary and genetic level of a representative sample of the population of Mallorca (Ob-IB study, N=493) have been carried out in order to analyse and identify factors that could explain the prevalence of obesity and the high cardiovascular risk in Mallorca. From the results obtained, a subset of 81 individuals, selected for their genetic, phenotypic and nutritional characteristics (OptiDiet-15 cohort), was re-contacted to further characterize the metabolism of their PBMC (peripheral blood cells). Cells were cultured and treated to evaluate, at molecular level, the modulating effect of the genotype/phenotype in their interaction with bioactive compounds of interest. -Research contents The study has shown that the population of Mallorca presents a phenotypic and nutritional profile similar to that of the Spanish population, but with genetic characteristics that could be key in the development of obesity and the prevalence of cardiovascular diseases. The greater presence of the obesity risk allele rs9939609 (FTO) in the population of Mallorca compared with the Spanish, would be a highlighting feature. Scores to estimate the genetic predisposition to the development of obesity (GenOb) and to the associated systemic inflammation (LGI-Ob) have been developed and applied to this population. This allowed to detect population subgroups at greater risk. Additionally, the analytical implementation of the LGI-Ob index would allow an early assessment of the predisposition to metabolic alterations before they develop phenotypically and would facilitate earlier prevention strategies. On the other hand, the study showed that the genetic baggage is able to modulate the relationship between dietary consumption of vitamin A (VA) and obesity in humans. The implication of the polymorphism (SNP) rs659366 (UCP2) in the differential risk of visceral obesity and type 2 diabetes has been observed, as well as the gene-nutrient-phenotype interaction, shown in the presence of this SNP and the sub-optimal intake of VA. In addition, the use of the ex vivo experimental approach, based on the PBMC (peripheral blood cells) from individuals selected for their genetic, nutritional and anthropometric characteristics, has enabled the characterization of the molecular bases and support the gene-nutrient-phenotype interaction; assessment of the impact on gene expression of VA derived compounds has been performed. -Conclusion Finally, the results derived from this Thesis may facilitate timely identification of individuals at higher risk and facilitate earlier implementation of nutritional strategies, optimized and adapted to the individual’s characteristics, and therefore, more effective to fight against obesity, being able to contribute to the maintenance of a healthy lifestyle throughout life.