Influence of diverse genetic polymorphisms on body weight and body composition during a weight loss program / influencia de diversos polimorfismos genéticos sobre el peso y la composición corporal durante un programa de pérdida de peso

Resumen

Introduction. Obesity is defined as an abnormal or excessive accumulation of fat that may impair health according to World Health Organization (WHO). Around the world it is every time more and more extended implying public health, economical and aesthetic problems. Researchers are trying to find the solution for the treatment or the prevention from different approaches such as diet, exercise, surgery, psychology, sociology what also shows its multifactorial causation. The genetic background of obesity has been proved by family and twin studies and up to date hundreds of genes have been identified to be related. However, today’s knowledge explains only a small part of the development of obesity far from the 40‐70% estimated for genetic influence on BMI. Obviously environmental factors are essential for weight loss and the prevention of obesity, but genetic information might help designing interventions in the future. Objectives. The objective of the present thesis was to study the influence of previously suggested candidate genes related to obesity on body weight and body composition variables, during and after a weight loss intervention. The main objective of the studies I and II was to examine if there were differences among genotype groups of the ADRB2 (Gln27Glu), ADRB3 (Trp64Arg), LEPR (Gln223Arg and Lys656Asn), and PPARG (Pro12Ala) genes during a controlled intervention in body weight, body mass index (BMI), fat mass, percentage fat, android fat or visceral adipose tissue. The secondary objective of the studies I and II was to evaluate the influence of these polymorphisms on baseline variables, body mass index and percentage fat. The objective of study III was to examine differences between MCT1 (Glu490Asp/T1470T) genotype groups in XXX body weight, BMI, percentage fat and percentage fat free mass. The objective of the study IV was to observe differences among genotype groups of the ADRB2 (Gln27Glu), ADRB3 (Trp64Arg), LEPR (Gln223Arg and Lys656Asn), MCT1 (Glu490Asp/T1470T) and PPARG (Pro12Ala) genes 3 years after a free living follow up in body weight, BMI, fat mass and percentage fat. Research design. This thesis is part of de Programas de Nutrición y Actividad Física para el Tratamiento de la Obesidad (PRONAF) project carried out in Spain. The PRONAF project was a clinical trial including 22‐week long controlled exercise and diet program. The weight loss intervention for overweight and obese participants applied a hypocaloric diet and aimed to compare different exercise protocols (supervised: strength, endurance, combined strength and endurance and non‐supervised: physical activity recommendations) in order to see which is the most effective. Strengthening the project, genetic polymorphisms related to obesity phenotypes were incorporated too. Results. Glu27 carriers of the ADRB2 gene in the supervised men group reduced weight and BMI more than the non‐carriers (p=0.019, 2.52 kg and p=0.019, 0.88 kg/m2 ). Non‐supervised women carrying of the Arg64 allele of the ADRB3 gene ended up with higher fat mass values than non‐carriers after the intervention (p=0.004, 7.22 kg). No differences were seen for body weight and body composition changes for the LEPR polymorphisms. Women non‐supervised carriers of the Ala12 allele of the PPARG gene reduced visceral adipose tissue (VAT) less than non‐carriers (p=0.024, 0.32 kg). No differences were found at baseline comparisons. Female non‐carriers of the A allele of the MCT1 gene reduced weight and BMI more than A allele carriers (p=0.004, 3.88 kg, XXXI effect size (ES) moderate and most likely positive and p=0.00037, 1.48 kg/m2 , ES large and most likely positive). In the female non‐supervised group A allele carriers of the MCT1 gene ended up with higher values of percentage fat (p=0.025, 1.94%), while the contrary in men, A allele carriers reduced fat more (p=0.037, 1.87%). In women non‐ carriers of the A allele of the MCT1 gene finished the program with higher percentage fat free mass values than the carriers of the A allele (p=0.005, 2.76%, ES small and possibly negative). In the follow up study, carriers of the Arg64 allele of the ADRB3 gene in men regained more weight and increased BMI more than non‐carriers, however effect size was unclear. Male carriers of the Arg223 allele of the LEPR gene had higher percentage fat values than non‐carriers, however effect size also was unclear. No other differences were seen between polymorphisms and follow up phenotypes. Conclusions. Conclusions of study I: The Gln27Glu polymorphism of the ADRB2 gene does not seem to influence weight or body composition changes. Arg64 allele of the ADRB3 gene in women might be disadvantageous in reducing fat mass and fat percentage during a weight loss program. Conclusions of study II: The Gln223Arg polymorphism and the Lys656Asn polymorphism of the LEPR gene does not seem have effect on influence weight or body composition changes. Ala12 allele might imply difficulty in losing visceral adipose tissue. The ADRB2 Gln27Glu, the ADRB3 Trp64Arg, LEPR Gln223Arg and Lys656Asn polymorphisms are not likely to influence baseline obesity phenotypes. Conclusions of study III: Carrying the Glu490 allele of the MCT1 gene might be related to smaller reductions in weight and BMI after a weight loss program. The Glu490 allele might be disadvantageous for women to lower percentage fat, but advantageous for men. Finally, the conclusions of the study IV: The Arg64 allele XXXII of the ADRB3 gene might be disadvantageous in weight maintenance in men. The Arg223 allele of the LEPR gene might facilitate body fat recovery in free‐living conditions in men. The ADRB2 Gln27Glu, the LEPR Lys656Asn, MCT1 Glu490Asp, PPARG Pro12Ala polymorphisms do not seem to influence body weight or fat regain after a 3 year follow up. Our results suggest that some of these polymorphism might affect body weight and body composition during a weight loss intervention and during subsequent 3‐year long follow up, however these effects are not determinant and results should be replicated.