Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children

Kilpeläinen, Tuomas O.; Qi, Lü; Brage, Sören; Sharp, Stephen J.; Sonestedt, Emily; Demerath, Ellen W.; Ahmad, Tariq; Mora, Samia; Kaakinen, Marika; Sandholt, Camilla H.; Holzapfel, Christina; Autenrieth, Christine S.; Hyppönen, Elina; Cauchi, Stéphane; He, Meian; Kutalik, Zoltán; Kumari, Meena; Stančáková, Alena; Meidtner, Karina; Balkau, Beverley; Tan, Jonathan T.; Mangino, Massimo; Timpson, Nicholas J.; Song, Yiqing; Zillikens, M. Carola; Jablonski, Kathleen A.; García, Melissa; Johansson, Stefan; Bragg‐Gresham, Jennifer L.; Wu, Ying; Vliet-Ostaptchouk, Jana V. van; Onland‐Moret, N. Charlotte; Zimmermann, Esther; Rivera, Natalia V.; Tanaka, Toshiko; Stringham, Heather M.; Silbernagel, Günther; Kanoni, Stavroula; Feitosa, Mary F.; Snitker, Søren; Ruiz, Jonatan R.; Metter, Jeffery; Larrad, Maria Teresa Martínez; Atalay, Mustafa; Hakanen, Maarit; Amin, Najaf; Cavalcanti-Proença, Christine; Grøntved, Anders; Hallmans, Göran; Jansson, John Olov; Kuusisto, Johanna; Kähönen, Mika; Lutsey, Pamela L.; Nolan, John J.; Palla, Luigi; Pedersen, Oluf; Pérusse, Louis; Renström, Frida; Scott, Robert A.; Shungin, Dmitry; Sovio, Ulla; Tammelin, Tuija; Rönnemaa, Tapani; Lakka, Timo A.; Uusitupa, Matti; Ríos, Manuel Serrano; Ferrucci, Luigi; Bouchard, Claude; Meirhaeghe, Aline; Fu, Mao; Walker, Mark; Borecki, Ingrid B.; Dedoussis, George; Fritsche, Andreas; Ohlsson, Claes; Boehnke, Michael; Bandinelli, Stefania; Duijn, Cornelia M. van; Ebrahim, Shah; Lawlor, Debbie A.; Gudnason, Vilmundur; Harris, Tamara B.; Sørensen, Thorkild I A; Mohlke, Karen L.; Hofman, Albert; Uitterlinden, André G.; Tuomilehto, Jaakko; Lehtimäki, Terho; Raitakari, Olli T.; Isomaa, Bo; Njølstad, Pål R.; Florez, José C.; Liu, Simin; Ness, Andy R; Spector, Timothy D.; Tai, E. Shyong; Froguel, Philippe; Boeing, Heiner; Laakso, Markku; Marmot, Michael; Bergmann, Sven; Power, Chris; Khaw, Kay Tee; Chasman, Daniel I.; Ridker, Paul M.; Hansen, Torben; Monda, Keri L.; Illig, Thomas; Järvelin, Marjo Riitta; Wareham, Nicholas J.; Hu, Frank B.; Groop, Leif; Orho‐Melander, Marju; Ekelund, Ulf; Franks, Paul W.; Loos, Ruth J.F.

doi:10.1371/journal.pmed.1001116

Cited by 468 publications

(501 citation statements)

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“…These fi ndings contrast with at least three studies which report no associations with energy intake in children (Hakanen et al, 2009;Okuda et al, 2011;Stutzmann et al, 2009) and to the observation in mice that FTO may modulate energy homeostasis through energy expenditure (Fischer et al, 2009;Speakman, 2010). However, several studies, including a large meta-analysis have recently shown that energy expenditure through activity appears to attenuate the genetic susceptibility to overweight and obesity from FTO in children Scott et al, 2010) and adults (Andreasen et al, 2008;Kilpelainen et al, 2011).…”

Section: Fat Mass and Obesity Associated Gene And Eating Behaviourcontrasting

confidence: 68%

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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The prevalence of childhood obesity is increasing in many countries and confers risks for early type 2 diabetes, cardiovascular disease and metabolic syndrome. In the presence of potent ' obesogenic ' environments not all children become obese, indicating the presence of susceptibility and resistance. Taking an energy balance approach, susceptibility could be mediated through a failure of appetite regulation leading to increased energy intake or via diminished energy expenditure. Evidence shows that heritability estimates for BMI and body fat are paralleled by similar coeffi cients for energy intake and preferences for dietary fat. Twin studies implicate weak satiety and enhanced food responsiveness as factors determining an increase in BMI. Single gene mutations, for example in the leptin receptor gene, that lead to extreme obesity appear to operate through appetite regulating mechanisms and the phenotypic response involves overconsumption and a failure to inhibit eating. Investigations of robustly characterized common gene variants of fat mass and obesity associated ( FTO ), peroxisome proliferator-activated receptor ( PPARG ) and melanocortin 4 receptor ( MC4R ) which contribute to variance in BMI also infl uence the variance in appetite factors such as measured energy intake, satiety responsiveness and the intake of palatable energy-dense food. A review of the evidence suggests that susceptibility to childhood obesity involving specifi c allelic variants of certain genes is mediated primarily through food consumption (appetite regulation) rather than through a decrease in activity-related energy expenditure. This conclusion has implications for early detection of susceptibility, and for prevention and management of childhood obesity.

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Section: Fat Mass and Obesity Associated Gene And Eating Behaviourcontrasting

confidence: 68%

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Cecil

Dalton

Finlayson

et al. 2012

International Review of Psychiatry

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“…It is well known that the association of FTO variants with BMI is observed more frequently in sedentary teenagers (16,17,47). In this population, the FTO gene showed an association in young people to the obesogenic factor of the time spent watching television and playing video games, as has occurred in other populations (17,43,48). We found a significant association between BMI and sedentary lifestyle, even after adjustment for physical activity.…”

Section: Discussionsupporting

confidence: 65%

“…The obesityassociated single nucleotide polymorphisms (SNP) are located in intron 1 of the FTO, all of which fall in a region of strong linkage disequilibrium (14); FTO encodes a protein that repairs alkylated DNA and RNA by oxidative demethylation (15); it has been implicated in increasing energy intake by regulating the expression of the genes that control appetite, such as leptin, leptin receptor, and neuropeptide Y (16). FTO has been associated with the modification of the degree of obesity in response to physical activity (17).…”

mentioning

confidence: 99%

Variante en CAPN10 y factores ambientales muestran evidencia de asociación con exceso de peso en jóvenes de Medellín, Colombia

et al. 2014

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participated in the study design, the fieldwork, the genetic and environmental information analysis and the writing of the article. Rosa M. Uscátegui conducted the anthropometric component of the study. María V. Parra conducted the genetic component. Introduction: Obesity results from interaction between genetic and environmental risk factors. Objective: To evaluate the effect of three gene variants and environmental factors on obesity and overweight in young people aged 10 to 18 years in a Colombian population. Materials and methods:A total of 424 subjects were selected and separated into three groups for a cross-sectional study; 100 obese and 112 overweight subjects were matched with 212 normal-weight controls. Associations were evaluated between excess weight and three genetic polymorphisms (UCP3-rs1800849, FTO-rs17817449, and CAPN10-rs3842570), as well as the family history, the time spent watching television and playing video games, and the diet. Results: A family history of obesity, the time spent watching television and playing video games, the lack of breastfeeding, a low consumption of cereals, legumes, fruits, vegetables, and a high consumption of fast foods were characteristics typically found in obese individuals compared to controls. A significant association between genotype I/I (SNP19 of CAPN10) and excess weight was found even with an active lifestyle. In addition, significant associations between the C/C genotype of the UCP3 gene and the G/G and T/T genotypes of the FTO gene and excess weight were found only in young sedentary individuals. Conclusions:In this population, inadequate diet and sedentary lifestyle increased the risk of excess weight. Genotype I/I of SNP19 in CAPN10 was significantly associated with excess weight. In contrast, FTO and UCP3 variants exhibited effects only in sedentary environments.

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“…1,2 The cause of obesity is multifactorial, for which genetics, environment, socioeconomic status, culture, and ethnicity are some primary factors. 3,4 Thus, the pathophysiology of obesity is a result of a complex interaction between environmental and genetic factors 5,6 that still are not fully delineated and understood. Obesity is defined as a body mass index (BMI) $30 and overweight as a BMI $25 in adults.…”

Section: Discussionmentioning

confidence: 99%

Uppsala Longitudinal Study of Childhood Obesity: Protocol Description

Forslund¹,

Staaf²,

Kullberg

et al. 2014

Pediatrics

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BACKGROUND AND OBJECTIVE: The prevalence of childhood obesity has risen considerably on a global scale during the past decades, and the condition is associated with increased risk of morbidity. The objective is to describe the Uppsala Longitudinal Study of Childhood Obesity (ULSCO) cohort, including some baseline data, and outline addressed research areas that aim at identifying factors implicated in and contributing to development of obesity and obesity-related diseases, including type 2 diabetes. METHODS: Severely obese and lean control subjects are examined at enrollment and at subsequent annual visits by using detailed questionnaires, anthropometric measurements, indirect calorimetry, and functional tests such as oral glucose tolerance tests. Some subjects undergo additional characterization with MRI, subcutaneous fat biopsies, frequent blood sampling, and hyperglycemic clamps. Biological samples are obtained and stored in a biobank. RESULTS: Active recruitment started in 2010, and standard operating procedures have been established. A high participation rate and annual follow-ups have resulted in a cohort exceeding 200 subjects, including 45 lean controls (as of October 2013). Initial research focus has been on traits of the metabolic syndrome, hyperinsulinemia and identifying risk factors for type 2 diabetes. CONCLUSIONS: The ULSCO cohort serves as an important resource in defining and understanding factors contributing to childhood obesity and development of obesity-related diseases. Given the comprehensive characterization of the cohort, factors contributing to disease development and progression can be identified. Such factors are further evaluated for their mechanistic role and significance, and noncommunicable metabolic diseases are especially addressed and considered.

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Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children

Cited by 468 publications

References 38 publications

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Obesity and eating behaviour in children and adolescents: Contribution of common gene polymorphisms

Variante en CAPN10 y factores ambientales muestran evidencia de asociación con exceso de peso en jóvenes de Medellín, Colombia

Uppsala Longitudinal Study of Childhood Obesity: Protocol Description

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