Nutrigenetic approaches for personalized management of obesity and metabolic syndrome traits

Altogether the results presented in this thesis clearly show that dietary and genetic factors could modulate susceptibility to obesity and its metabolic disorders. Notably, individuals with a high genetic predisposition to obesity, defined by a GRS based on 16 obesity and lipid metabolism related polymorphisms, showed higher adiposity measures and obesity risk than those individuals with a low genetic predisposition. Although scientific evidence suggests the heritability component of obesity, in the present study we observed that genetic factors explain a small percentage of BMI variation as has been found by other authors. However, when we include in the regression model phenotypic features such as age, physical activity and energy intake the percentage of BMI explanation increased. These results confirm that obesity should be treated as a multifactorial disease in which a large number of phenotypic and genotypic factors are involved. Furthermore, our research work also contributes to better understand not only the role of genetics on body weight loss but also how the diet could modify the association between a polymorphism and body weight regulation. Specifically, for the first time we reported the interaction between the ADCY3 rs10182181 genetic variant and dietary macronutrient distribution on changes in anthropometric and body composition measurements. In addition, the MTNR1B rs101830963 genetic variant interacted with dietary fat intake in response to a hypocaloric diet in terms of body composition and lipid metabolism traits. On the other hand, the fat/carbohydrate intake modified the association between the PPM1K rs1440581 variant and changes in insulin and insulin resistance traits after a dietary intervention to induced weight loss. Finally, the association between the NOS3 rs1799983 polymorphism and DBP and risk of hypertension was modified by MUFA and PUFA intake, and BMI, respectively. Nutrigenetics emerges as a good option to further investigate the interindividual susceptibility to metabolic disorders and the response to dietary interventions, and therefore provide personalized nutrition based on the genetic make-up for preventing and treating obesity and its related comorbidities.