Controlled exercise as a tool for preventing obesity and metabolic diseases in Arg64 carrier women.

Genética y ejercicio

Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention

The β-2 and β-3 adrenergic receptors (ADRB2 and ADRB3) are thought to play a role in energy expenditure and lipolysis. However, the effects of the ADRB2 glutamine (Gln) 27 glutamic acid (glutamate) (Glu) and ADRB3 tryptophan (Trp) 64 arginine (Arg) polymorphisms on weight loss remain controversial. The aim of this study was to investigate the effect of these polymorphisms on changes in weight and body composition during a controlled weight-loss program. One hundred seventy-three healthy overweight and obese participants (91 women, 82 men) aged 18–50 years participated in a 22-week-long intervention based on a hypocaloric diet and exercise. They were randomly assigned to 1 of 4 groups: strength, endurance, strength and endurance combined, and physical activity recommendations only. Body weight, body mass index (BMI), and body composition variables were assessed before and after the intervention. Genetic analysis was carried out according to standard protocols. No effect of the ADRB2 gene was shown on final weight, BMI, or body composition, although in the supervised male group, Glu27 carriers tended to have greater weight (p = 0.019, 2.5 kg) and BMI (p = 0.019, 0.88 kg/m2) reductions than did noncarriers. There seems to be an individual effect of the ADRB3 polymorphism on fat mass (p = 0.004) and fat percentage (p = 0.036), in addition to an interaction with exercise for fat mass (p = 0.038). After the intervention, carriers of the Arg64 allele had a greater fat mass and fat percentage than did noncarriers (p = 0.004, 2.8 kg). In conclusion, the ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms may influence weight loss and body composition, although the current evidence is weak; however, further studies are necessary to clarify their roles. </jats:p

Influence of ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms on body weight and body composition changes after a controlled weight-loss intervention

The ?-2 and ?-3 adrenergic receptors (ADRB2 and ADRB3) are thought to play a role in energy expenditure and lipolysis. However, the effects of the ADRB2 glutamine (Gln) 27 glutamic acid (glutamate) (Glu) and ADRB3 tryptophan (Trp) 64 arginine (Arg) polymorphisms on weight loss remain controversial. The aim of this study was to investigate the effect of these polymorphisms on changes in weight and body composition during a controlled weight-loss program. One hundred seventy-three healthy overweight and obese participants (91 women, 82 men) aged 18?50 years participated in a 22-week-long intervention based on a hypocaloric diet and exercise. They were randomly assigned to 1 of 4 groups: strength, endurance, strength and endurance combined, and physical activity recommendations only. Body weight, body mass index (BMI), and body composition variables were assessed before and after the intervention. Genetic analysis was carried out according to standard protocols. No effect of the ADRB2 gene was shown on final weight, BMI, or body composition, although in the supervised male group, Glu27 carriers tended to have greater weight (p = 0.019, 2.5 kg) and BMI (p = 0.019, 0.88 kg/m2) reductions than did noncarriers. There seems to be an individual effect of the ADRB3 polymorphism on fat mass (p = 0.004) and fat percentage (p = 0.036), in addition to an interaction with exercise for fat mass (p = 0.038). After the intervention, carriers of the Arg64 allele had a greater fat mass and fat percentage than did noncarriers (p = 0.004, 2.8 kg). In conclusion, the ADRB2 Gln27Glu and ADRB3 Trp64Arg polymorphisms may influence weight loss and body composition, although the current evidence is weak; however, further studies are necessary to clarify their roles

Impacto del alelo APOE2 en el cambio del perfil lipídico después de un programa de pérdida de peso

Background: apolipoprotein E (ApoE) polymorphism is a genetic determinant of lipid and lipoprotein levels and the risk for coronary heart disease. Objective: to evaluate the impact of ApoE2 allele in lipid plasma levels and the influence of a healthy hypocaloric diet plus a controlled physical activity on the lipid profile, we performed a study in a cohort of overweight and obese healthy subjects (Body Mass Index (BMI) between 25 and 34.9 kg·m-2). Methods: one hundred eighty participants (96 women), aged 18-50 years participated in a 22 weeks weight loss intervention based on same dietary treatment and different controlled exercise programs. All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure). Blood samples were obtained for lipids measurements at the beginning and end of the study. Results: after intervention, men of the E2 group showed the greatest decreases in low-density lipoprotein (LDL), triglycerides (TG) and total cholesterol (TC) values (p = 0.039; p = 0.001; p = 0.001; respectively). For high-density lipoprotein (HDL), E2 group had significant differences compared with E4 at pre- (p = 0.020) and post-intervention values (p = 0.024). Conclusion: our results show great changes in men carrying ApoE2, mainly in TG and TC concentrations after treatment with hypocaloric diet and controlled exercise. Therefore, adding supervised training to nutritional intervention seems to be a good alternative for the reinforcement of the effect of the treatment.Antecedentes: el polimorfismo de la apolipoproteína E (ApoE) es un determinante genético de los niveles de lípidos y lipoproteínas y el riesgo de enfermedad coronaria. Objetivo: para evaluar el impacto del alelo ApoE2 en los niveles de lípidos plasmáticos y la influencia de una dieta hipocalórica sana más una actividad física controlada en el perfil lipídico, se realizó un estudio en una cohorte de sujetos sanos con sobrepeso y obesidad (índice de masa corporal entre 25-34,9 kg·m-2). Métodos: ciento ochenta participantes (96 mujeres), de 18-50 años participaron en una intervención de pérdida de peso de 22 semanas basada en el mismo tratamiento dietético y diferentes programas de ejercicios controlados. Todos los sujetos siguieron una dieta hipocalórica (consumo de energía entre 25-30% inferior que el gasto energético total diario). Se obtuvieron muestras de sangre para las mediciones de lípidos al inicio y al final del estudio. Resultados: después de la intervención, los hombres del grupo E2 mostraron las mayores disminuciones en los valores de lipoproteína de baja densidad (LDL), triglicéridos (TG) y colesterol total (TC) (p = 0,039; p = 0,001; p = 0,001). Para las lipoproteínas de alta densidad (HDL), el grupo E2 presentó diferencias significativas en comparación con E4 en los valores previos (p = 0,020) y postintervención (p = 0,024). Conclusión: nuestros resultados muestran grandes cambios en los hombres que portan ApoE2, principalmente en las concentraciones de TG y TC después del tratamiento con dieta hipocalórica y ejercicio controlado. Por lo tanto, la adición de entrenamiento supervisado a la intervención nutricional parece ser una buena alternativa para el refuerzo del efecto del tratamiento.FUNDING SOURCE: The PRONAF Study took place with the financial support of the Ministerio de Ciencia e Innovación, Convocatoria de Ayudas I+D 2008, Proyectos de Investigación Fundamental No Orientada, del VI Plan de Investigación Nacional 2008-2011, (Contract: DEP2008-06354-C04-01). We acknowledge and thank all of the subjects who participated in the study. We thank Víctor Díaz Molina, PhD for valuable discussion

Nutrition and physical activity programs for obesity treatment (PRONAF study). methodological approach of the project

Este trabajo aborda la metodología seguida para llevar a cabo el proyecto de investigación PRONAF (Clinical Trials Gov.: number NCT01116856.) Background: At present, scientific consensus exists on the multifactorial etiopatogenia of obesity. Both professionals and researchers agree that treatment must also have a multifactorial approach, including diet, physical activity, pharmacology and/or surgical treatment. These two last ones should be reserved for those cases of morbid obesities or in case of failure of the previous ones. The aim of the PRONAF study is to determine what type of exercise combined with caloric restriction is the most appropriate to be included in overweigth and obesity intervention programs, and the aim of this paper is to describe the design and the evaluation methods used to carry out the PRONAF study. Methods/design: One-hundred nineteen overweight (46 males) and 120 obese (61 males) subjects aged 18–50 years were randomly assigned to a strength training group, an endurance training group, a combined strength + endurance training group or a diet and physical activity recommendations group. The intervention period was 22 weeks (in all cases 3 times/wk of training for 22 weeks and 2 weeks for pre and post evaluation). All subjects followed a hypocaloric diet (25-30% less energy intake than the daily energy expenditure estimated by accelerometry). 29–34% of the total energy intake came from fat, 14–20% from protein, and 50–55% from carbohydrates. The mayor outcome variables assesed were, biochemical and inflamatory markers, body composition, energy balance, physical fitness, nutritional habits, genetic profile and quality of life. 180 (75.3%) subjects finished the study, with a dropout rate of 24.7%. Dropout reasons included: personal reasons 17 (28.8%), low adherence to exercise 3 (5.1%), low adherence to diet 6 (10.2%), job change 6 (10.2%), and lost interest 27 (45.8%). Discussion: Feasibility of the study has been proven, with a low dropout rate which corresponds to the estimated sample size. Transfer of knowledge is foreseen as a spin-off, in order that overweight and obese subjects can benefit from the results. The aim is to transfer it to sports centres. Effectiveness on individual health-related parameter in order to determine the most effective training programme will be analysed in forthcoming publications

Influence of diverse genetic polymorphisms on body weight and body composition during a weight loss program

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 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 Glu490 allele of the MCT1 gene reduced weight and BMI more than Glu490 allele carriers (p=0.004, 3.88 kg, 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 Glu490 allele carriers of the MCT1 gene ended up with higher values of percentage fat (p=0.025, 1.94%), while the contrary in men, Glu490 allele carriers reduced fat more (p=0.037, 1.87%). In women non-carriers of the Glu490 allele of the MCT1 gene finished the program with higher percentage fat free mass values than the carriers of the Glu490 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 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. ----------RESUMEN---------- Introducción. La obesidad se define como una acumulación anormal o excesiva de grasa que puede perjudicar la salud según la Organización Mundial de la Salud. En todo el mundo se extiende cada vez más, lo que implica problemas de salud pública, económicos y estéticos. Los investigadores están tratando de encontrar la solución para el tratamiento y la prevención de diferentes enfoques como la dieta, el ejercicio, la cirugía, la psicología, la sociología, lo que también muestra su causalidad multifactorial. Las bases genéticas de la obesidad han sido demostradas por estudios de familias y gemelos y hasta la fecha se han identificado cientos de genes relacionados. Sin embargo, el conocimiento de hoy sólo explica una pequeña parte del desarrollo de la obesidad, lejos del 40-70% estimado para la influencia genética en el índice de masa corporal. Obviamente, los factores ambientales son esenciales para la pérdida de peso y la prevención de la obesidad, pero la información genética podría ayudar a diseñar intervenciones en el futuro. Objetivos. El objetivo de la presente tesis fue estudiar la influencia de genes candidatos previamente sugeridos relacionados con la obesidad en el peso corporal y las variables de composición corporal, durante y después de una intervención de pérdida de peso. El objetivo principal de los estudios I y II fue examinar si había diferencias entre los grupos de genotipo de los genes ADRB2 (Gln27Glu), ADRB3 (Trp64Arg), LEPR (Gln223Arg y Lys656Asn) y PPARG (Pro12Ala) durante una intervención controlada en peso corporal, índice de masa corporal, masa grasa, porcentaje de grasa, grasa androide o tejido adiposo visceral. El objetivo secundario de estos estudios fue evaluar la influencia de estos polimorfismos sobre las variables basales, el índice de masa corporal (IMC) y el porcentaje de grasa. El objetivo del estudio III fue examinar diferencias entre grupos genéticos del polimorfismo MCT1 (Glu490Asp/T1470T) en peso corporal, IMC, porcentaje de grasa y porcentaje de masa magra. El objetivo principal del estudio IV fue observar las diferencias entre los grupos genéticos de los genes ADRB2 (Gln27Glu), ADRB3 (Trp64Arg), LEPR (Gln223Arg y Lys656Asn), MCT1 (Glu490Asp) y PPARG (Pro12Ala) durante un seguimiento de 3 años en peso corporal, IMC, masa grasa y porcentaje de grasa. Diseño de la investigación. Esta tesis es parte del proyecto de Programas de Nutrición y Actividad Física para el Tratamiento de la Obesidad (PRONAF) realizado en España. El proyecto PRONAF fue un ensayo clínico que incluyó un programa controlado de ejercicio y dieta de 22 semanas de duración. La intervención de pérdida de peso para participantes con sobrepeso y obesidad aplicó una dieta hipocalórica y tuvo como objetivo comparar diferentes protocolos de ejercicio (supervisado: fuerza, resistencia, fuerza combinada y resistencia y no supervisado: recomendaciones de actividad física) para ver cuál es el más eficaz. Fortaleciendo el proyecto, se incorporaron polimorfismos genéticos relacionados con la obesidad. Resultados. Portadores del Glu27 del gen ADRB2 en el grupo supervisado de hombres reducieron el peso corporal y el IMC más que los no-portadores (p=0.019, 2.52 kg y p=0.019, 0.88 kg/m2). Mujeres no-supervisadas con el alelo Arg64 del gen ADRB3 terminaron el programa con valores mayores en masa grasa que los no portadores (p=0.004, 7.22 kg). No había diferencias en cambio de peso o composición corporal en los polimorpfismos de LEPR. Mujeres no-supervisadas con el alelo Ala12 del gen PPARG bajaron el tejido adiposo visceral menos que los no-portadores (p=0.024, 0.32 kg). No se encontraron diferencias en las comparaciones de los valores basales. Mujeres no- portadores del alelo A del gen MCT1 bajaron el peso y el IMC más que los portadores (p=0.004, 3.88 kg, tamaño del efecto moderado y lo más probable positivo y p=0.00037, 1.48 kg/m2, tamaño del efecto grande y lo más probable positivo). Dentro de las mujeres no-supervisadas portadoras del alelo A del gen MCT1 terminaron el programa con valores mayores de porcentaje de grasa (p=0.025, 1.94%), pero el contrario en hombres, los portadores del alelo A bajaron más el porcentaje de grasa (p=0.037, 1.87%). Mujeres no portadoras del alelo A del gen MCT1 acabaron la intervención con más porcentaje de masa magra que los portadores (p=0.005, 2.76%, tamaño del efecto pequeño y possible negativo). En el estudio de seguimiento, portadores del alelo Arg64 del gen ADRB3 en hombres recuperaron más peso e incrementaron el IMC más que los no-portadores, aunque el tamaño del efecto fue dudoso. Hombres con el alelo Arg223 del gen LEPR tuvieron valores de porcentaje de grasa mayores que los no-portadores aunque el tamaño del efecto fue dudoso también. No se encontraron otras diferencias entre polimorfismos y fenotipos del seguimiento. Conclusiones. Conclusiones del estudio I: El polimorfismo Gln27Glu del gen ADRB2 no parece influir los cambios de peso corporal o composición corporal. El alelo Arg64 del gen ADRB3 en mujeres puede ser desventajoso para reducir masa grasa y porcentaje de grasa durante un programa de pérdida de peso. Conclusiones del estudio II: Los polimorfismos Gln223Arg y Lys656Asn del gen LEPR no parecen influir en los cambios de peso corporal o composición corporal. El alelo Ala12 del gen PPARG podría implicar dificultad en perder tejido adiposo visceral. No es probable que los polimorfismos ADRB2 Gln27Glu, ADRB3 Trp64Arg, LEPR Gln223Arg y Lys656Asn influyen fenotipos basales relacionados a la obesidad. Conclusiones del estudio III: Tener el alelo Glu490 del gen MCT1 puede ser relacionada a reducciones menores en peso corporal y IMC después de un programa de pérdida de peso. El alelo Glu490 puede ser desventajoso para mujeres para bajar porcentaje de grasa, pero ventajoso para hombres. Finalmente, las conclusiones del estudio IV: El alelo Arg64 del gen ADRB3 puede ser desventajoso en mantener el peso corporal. El alelo Arg223 del gen LEPR puede facilitar la recuperación de grasa corporal durante el seguimiento en hombres. Los polimorfismos ADRB2 Gln27Glu, LEPR Lys656Asn, MCT1 Glu490Asp y PPARG Pro12Ala no parecen influir la recuperación de peso corporal o masa grasa después de un seguimiento de 3 años. Nuestros resultados sugieren que algunos de estos polimorfismos pueden afectar el peso corporal y la composición corporal durante una intervención de pérdida de peso y durante el seguimiento posterior de 3 años, sin embargo estos efectos no son determinantes y deben ser replicados

Comparison between different methods for measuring body fat after a weight loss program = Comparação entre diferentes métodos para mensuração da gordura corporal após um programa de perda de peso

Introduction. Accurate and sensitive measurement of body composition is an important tool in the diagnosis and control of obesity. Objective. To compare body fat changes measured by dual-energy X-ray absorptiometry (DXA), bioelectrical impedance analysis (BIA), and skinfolds (SK) in healthy overweight adults in order to evaluate whether all three methods can be used during a weight loss program (WLP). Methods. Eighty-four men (n=36) and women (n=48), body mass index 25–29.9 kg/m2, aged between 18-50 years, non-smokers and sedentary, were randomly assigned to strength, endurance, combined strength plus endurance, or physical activity recommendations groups. All subjects followed a hypocaloric diet (25-30% decrease in energy intake in terms of the total daily energy expenditure). The intervention lasted 22 weeks. Results. The highest correlation was obtained between DXA and SK when men and women were studied together (r=0.864, p0.05) when changes in body fat caused by intervention were analyzed. However, considering results of the minimal difference compared to DXA, BIA showed the greatest sensitivity to detect changes in fat percentage and fat mass, while SK underestimated the changes, with a significantly lower percentage considered real (p=0.01). Conclusion. The SK method seems to underestimate real changes, therefore DXA and BIA can serve as more effective tools to measure the change in fat percentage and fat mass during WLP. Level of evidence II, Diagnosis. Introdução. A mensuração precisa e sensível da composição corporal é uma importante ferramenta para o diagnóstico e controle da obesidade. Objetivo. Comparar as alterações da gordura corporal mensuradas através da absorciometria com raios-X de dupla energia (DEXA), análise da impedância bioelétrica (BIA) e dobras cutâneas (DC) em adultos saudáveis com sobrepeso, a fim de avaliar se os três métodos podem ser utilizados durante um programa de perda de peso (PPP). Métodos. Oitenta e quatro homens (n=36) e mulheres (n=48) com índice de massa corporal entre 25-29,9 kg/m2, idade entre 18-50 anos, não-fumantes e sedentários foram divididos aleatoriamente em grupos de de força, resistência, combinados de força mais resistência ou com recomendações de atividade física. Todos os indivíduos seguiram uma dieta hipocalórica (25-30% de redução na ingestão energética em relação ao gasto energético total diário). A intervenção durou 22 semanas. Resultados. A maior correlação foi obtida entre a DEXA e DC quando homens e mulheres foram estudados juntos (r=0,864, p0,05) quando foram analisadas alterações na gordura corporal ocasionadas pela intervenção. No entanto, considerando os resultados da mínima diferença comparados à DEXA, a BIA apresentou maior sensibilidade para detectar mudanças no percentual de gordura e massa gorda, enquanto a DC subestimou as mudanças, com um percentual significativamente mais baixo considerado real (p=0,01). Conclusão. O método de DC parece subestimar as mudanças reais, portanto, a DEXA e BIA podem ser ferramentas mais eficazes para mensurar a alteração no percentual de gordura e a massa gorda durante um PPP. Nível de evidência II, Diagnóstico

Research concept for the study of implementation

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