Lunch eating predicts weight-loss effectiveness in carriers of the common allele at PERILIPIN1: the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study

Authors: GARAULET, MARTA - UNIVERSIDAD DE MURCIA; VERA, BEATRIZ - UNIVERSIDAD DE MURCIA; BONNET-RUBIO, GEMMA - UNIVERSIDAD DE MURCIA; GÓMEZ-ABELLÁN, PURIFICACIÓN - UNIVERSIDAD DE MURCIA; LEE, YU-CHI - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY; ORDOVAS, JOSE - JEAN MAYER HUMAN NUTRITION RESEARCH CENTER ON AGING AT TUFTS UNIVERSITY

Submitted to: The American Journal of Clinical Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/8/2016
Publication Date: 9/14/2016
Citation: Garaulet, M., Vera, B., Bonnet-Rubio, G., Gómez-Abellán, P., Lee, Y., Ordovas, J.M. 2016. Lunch eating predicts weight-loss effectiveness in carriers of the common allele at PERILIPIN1: the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study. American Journal of Clinical Nutrition. doi: 10.3945/ajcn.116.134528.

Interpretive Summary: Nutritional recommendations and guidelines have focused on the consumption of macronutrients and micronutrients in terms of relative and absolute amounts. However, recent research by us and other investigators have shown that when we eat is also an important factor for our overall health and specifically to maintain or regain healthy body weight. In this regard, the synchronization between our central biological clock in the brain and those in the peripheral tissues (i.e. adipose tissue) may be essential to coordinate fat mobilization. One of the most important regulators of this mobilization is a protein known as Perilipin 1 (PLIN1,) which we have previously shown plays an important role in human obesity. Our objective in this work was to investigate the relation between genetic variability at the PLIN1 locus, time of food intake, and anthropometric measures as well as the ability to lose weight enrolled in a weight loss program (n>/=1,287.) Our results show that variability at the PLIN1 locus was associated with weight loss. Moreover, eating late resulted in less successful weight loss among those who were carriers of the AA genotype at the PLIN1 14995A>T polymorphism. Our results will contribute to more precise recommendations to increment the success of weight loss programs by taking into consideration both genetic and chronobiology factors.

Technical Abstract: Background: We propose that eating lunch late impairs the mobilization of fat from adipose tissue, particularly in carriers of PERILIPIN1 (PLIN1) variants. Objective: The aim was to test the hypothesis that PLIN1, a circadian lipid-stabilizing protein in the adipocyte, interacts with the timing of food intake to affect weight loss. Design: A total of 1287 overweight and obese subjects [229 men and 1058 women; mean +/- SD body mass index (in kg/m2): 31 +/- 5] who attended outpatient obesity clinics were enrolled in the ONTIME (Obesity, Nutrigenetics, Timing, Mediterranean) study. Timing of food intake was estimated with a validated questionnaire. Anthropometric variables and PLIN1 genotypes were analyzed, including 6209T>C (rs2289487), 11482G>A (rs894160), 13041A>G (rs2304795), and 14995A>T (rs1052700). The main outcomes were effectiveness of the program and weight-loss progression during 28 wk of treatment. Results: The PLIN1 locus was associated with variability in response to a weight-loss program. Specifically, carrying the minor C allele at the PLIN1 6209T>C was associated with better weight-loss response (P = 0.035). The probability of being a better responder [percentage of weight loss >/= 7.5% (median)] was 33% higher among C than among TT carriers (OR: 1.32; 95% CI: 1.05, 1.67; P = 0.017). We found an interaction of PLIN1 x food timing between the 14995A>T variant and timing of lunch eating for total weight loss (P = 0.035). Among AA carriers, eating late was associated with less weight loss (P >0.001), whereas time of eating did not influence weight loss among TT carriers (P = 0.326). Conclusions: Variability at the PLIN1 locus is associated with variability in weight loss. Moreover, eating late is related to lower weight-loss effectiveness among carriers of the AA genotype at the PLIN1 14995A>T variant. These results contribute to our ability to implement more precise and successful obesity treatments.