La nutrigenética en el tratamiento personalizado de la obesidad y del riesgo metabólico. Estudio ontime (obesidad, nutrigenética, tiempo, mediterránea)

Abstract

Nutrigenetics in the personalized treatment of obesity and metabolic risk. ONTIME (Obesity, Nutrigenetics, TIempo, MEditerranean) study. Objetives The objectives of the present doctoral thesis were the following: 1. To show that PLIN1 SNPs are associated with weight loss in participants in a dietary treatment based on Mediterranean diet and to investigate food timing (breakfast, lunch, and dinner) and PLIN1 genotype interactions for weight loss. 2. Determine whether one allelic promoter variant of the serotonin transporter gene (SLC6A4) relates to emotional eating, or to the ability to control the amount of food eaten in an overweight/obese population subjected to a behavioral/dietary treatment for obesity; this association could affect total weight loss. 3. Examine the behavioral and emotional factors related to food within the same population (ONTIME population). Finally, and most importantly, investigate the contribution of factors such as genetics, lifestyle and circadian physiological characteristics in the connection of the evening chronotype with risk of metabolic syndrome. Design: In this doctoral thesis we have studied overweight and obese subjects who attended outpatient obesity nutrition clinics and were enrolled in the ONTIME (Obesity, Nutrigenetics, Timing, MEditerranean) study. The ONTIME study was registered at clinicaltrials.gov as NCT02829619. In the first study, anthropometric variables and PLIN1 genotypes were analyzed, including 6209T>C (rs2289487), 11482G>A (rs894160), 13041A>G (rs2304795), and 14995A>T (rs1052700). Timing of food intake was estimated with a validated questionnaire. In the second study, total weight-loss, emotional-eating score and disinhibition-score were examined. A subsample (n=624) was recruited for SLC6A4 genotyping. Finally, in the third study, chronotype, a genetic-risk-score (GRS), comprised of 15 chronotype-related variants, was tested. Moreover, a wide range of behavioral and emotional eating factors was studied within the same population. Conclusions: 1. We show that variability at the PLIN1 locus is associated with variability in weight loss in subjects subjected to a dietary-behavioral treatment. On the other hand, we identified a PLIN1*food timing interaction between 14995A>T and timing of lunch eating for total weight loss. Among major allele AA carriers, those who ate lunch later (>3:00 p.m.) lost significantly less weight than did those who ate earlier. We support the idea of identifying PLIN1 genotypes in patients to determine the effectiveness of weight loss treatment. 2. SLC6A4-promoter variant is associated with the ability to control food intake in an obese or overweight population undergoing dietary-behavioral treatment. Besides, SLC6A4 interacts with emotional eating and disinhibition behaviors to modulate total weight-loss. Carriers of allele S of SLC6A4 who are emotional with food or have a high disinhibition have greater difficulty in losing weight during dietary treatment. Conducting a genetic and psychosocial assessment prior to dietary treatment could improve the effectiveness of weight loss for obese or overweight people. 3. The evening chronotype is associated with a high risk of metabolic syndrome. We confirm this risk is not due to genetics but to their lifestyle, especially sedentary lifestyle and obesogenic feeding behaviors. Therefore, cognitive therapies should be implanted to make a behavioral change in the evening chronotype and thus reverse or prevent metabolic disorders.