Fat Mass and Obesity-Associated (FTO) Gene Polymorphisms Are Associated with Physical Activity, Food Intake, Eating Behaviors, Psychological Health, and Modeled Change in Body Mass Index in Overweight/Obese Caucasian Adults

The fat mass and obesity-associated (FTO) gene is currently recognized as the most robust predictor of polygenic obesity. We investigated associations between the FTO rs1421085 and rs17817449 polymorphisms and the FTO rs1421085–rs17817449 haplotype and dietary intake, eating behavior, physical activity, and psychological health, as well as the effect of these associations on BMI. N = 133 treatment seeking overweight/obese Caucasian adults participated in this study. Genotyping was performed from whole blood samples. Weight and height was measured and a non-quantified food frequency questionnaire was completed to assess food group intake. Validated questionnaires were completed to assess physical activity (Baecke questionnaire), psychological health (General Health questionnaire, Rosenburg self-esteem scale and Beck Depression Inventory), and eating behavior (Three Factor Eating questionnaire). The risk alleles of the FTO polymorphisms were associated with poorer eating behaviors (higher hunger, internal locus for hunger, and emotional disinhibition scores), a higher intake of high fat foods and refined starches and more depressive symptoms. The modeled results indicate that interactions between the FTO polymorphisms or haplotypes and eating behavior, psychological health, and physical activity levels may be associated with BMI. The clinical significance of these results for implementation as part of weight management interventions needs further investigation.

[1]  L. Birch,et al.  Dieting, restraint, and disinhibition predict women's weight change over 6 y. , 2009, The American journal of clinical nutrition.

[2]  Inês Barroso,et al.  The genetics of obesity: FTO leads the way , 2010, Trends in genetics : TIG.

[3]  J. M. Cattell,et al.  The Psychological Corporation , 1923, Science.

[4]  M. Banks Validation of the General Health Questionnaire in a young community sample , 1983, Psychological Medicine.

[5]  I. Romao,et al.  Genetic and environmental interactions in obesity and type 2 diabetes. , 2008, Journal of the American Dietetic Association.

[6]  M. Jarvelin,et al.  A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult Obesity , 2007, Science.

[7]  A. Stunkard,et al.  The Eating Inventory, body adiposity and prevalence of diseases in a quota sample of Czech adults , 2006, International Journal of Obesity.

[8]  M. Rosenberg Society and the adolescent self-image , 1966 .

[9]  G. Yeo,et al.  FTO expression is regulated by availability of essential amino acids , 2013, International Journal of Obesity.

[10]  M. McCarthy,et al.  Regulation of Fto/Ftm gene expression in mice and humans. , 2008, American journal of physiology. Regulatory, integrative and comparative physiology.

[11]  Chengqi Yi,et al.  Oxidative demethylation of 3‐methylthymine and 3‐methyluracil in single‐stranded DNA and RNA by mouse and human FTO , 2008, FEBS letters.

[12]  Swneke D. Bailey,et al.  Genetic Variants of FTO Influence Adiposity, Insulin Sensitivity, Leptin Levels, and Resting Metabolic Rate in the Quebec Family Study , 2008, Diabetes.

[13]  C. Mobbs,et al.  Impaired hypothalamic Fto expression in response to fasting and glucose in obese mice , 2011, Nutrition & Diabetes.

[14]  A. Stunkard,et al.  The Eating Inventory in obese women: Clinical correlates and relationship to weight loss , 1998, International Journal of Obesity.

[15]  T. Hansen,et al.  Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity. , 2008, Journal of Clinical Endocrinology and Metabolism.

[16]  L. V. Van Gaal,et al.  Variants in the FTO gene are associated with common obesity in the Belgian population. , 2008, Molecular genetics and metabolism.

[17]  Beverley Balkau,et al.  Variation in FTO contributes to childhood obesity and severe adult obesity , 2007, Nature Genetics.

[18]  Ryan T. Pitman,et al.  Knockdown of the Fat Mass and Obesity Gene Disrupts Cellular Energy Balance in a Cell-Type Specific Manner , 2012, PloS one.

[19]  F. Ashcroft,et al.  Adult Onset Global Loss of the Fto Gene Alters Body Composition and Metabolism in the Mouse , 2013, PLoS genetics.

[20]  Qiang Wang,et al.  Crystal structure of the FTO protein reveals basis for its substrate specificity , 2010, Nature.

[21]  Chris P. Ponting,et al.  The Obesity-Associated FTO Gene Encodes a 2-Oxoglutarate-Dependent Nucleic Acid Demethylase , 2007, Science.

[22]  J. Hoffstedt,et al.  The common rs9939609 gene variant of the fat mass- and obesity-associated gene FTO is related to fat cell lipolysis Published, JLR Papers in Press, November 29, 2007. , 2008, Journal of Lipid Research.

[23]  Peter Dalgaard,et al.  R Development Core Team (2010): R: A language and environment for statistical computing , 2010 .

[24]  S. Barr,et al.  "Restrained eating" vs "trying to lose weight": how are they associated with body weight and tendency to overeat among postmenopausal women? , 2009, Journal of the American Dietetic Association.

[25]  Murat Baş,et al.  Self-efficacy and restrained eating in relation to weight loss among overweight men and women in Turkey , 2009, Appetite.

[26]  James O. Hill,et al.  Obesity and the Environment: Where Do We Go from Here? , 2003, Science.

[27]  S. O’Rahilly,et al.  Hypothalamic-Specific Manipulation of Fto, the Ortholog of the Human Obesity Gene FTO, Affects Food Intake in Rats , 2010, PloS one.

[28]  Tanya M. Teslovich,et al.  Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index , 2010 .

[29]  Boyd Swinburn,et al.  Diet, nutrition and the prevention of chronic diseases : report of a Joint WHO/FAO Expert Consultation , 2003 .

[30]  A. Stunkard,et al.  The three-factor eating questionnaire to measure dietary restraint, disinhibition and hunger. , 1985, Journal of psychosomatic research.

[31]  I. Craig,et al.  The protective effect of the obesity-associated rs9939609 A variant in fat mass- and obesity-associated gene on depression , 2013, Molecular Psychiatry.

[32]  S Sanderson,et al.  The FTO gene and measured food intake in children , 2009, International Journal of Obesity.

[33]  J. Blundell,et al.  Disinhibition: its effects on appetite and weight regulation , 2007, Obesity reviews : an official journal of the International Association for the Study of Obesity.

[34]  M. Lorr,et al.  Two objective measures of self-esteem. , 1986, Journal of personality assessment.

[35]  W. Reynolds Measurement of Academic Self-Concept in College Students , 1988 .

[36]  D. Albanes,et al.  Validation and Comparison of Eight Physical Activity Questionnaires , 1990, Epidemiology.

[37]  D. Goldberg The detection of psychiatric illness by questionnaire : a technique for the identification and assessment of non-psychotic psychiatric illness , 1972 .

[38]  Shirley A. Miller,et al.  A simple salting out procedure for extracting DNA from human nucleated cells. , 1988, Nucleic acids research.

[39]  P. Björntorp,et al.  Depression and anxiety symptoms in relation to anthropometry and metabolism in men , 2002, Psychiatry Research.

[40]  H. Schiöth,et al.  The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. , 2008, Endocrinology.

[41]  L. Sánchez-Pulido,et al.  The FTO (fat mass and obesity associated) gene codes for a novel member of the non-heme dioxygenase superfamily , 2007, BMC Biochemistry.

[42]  E. Demerath,et al.  Physical Activity Attenuates the Influence of FTO Variants on Obesity Risk: A Meta-Analysis of 218,166 Adults and 19,268 Children , 2011, PLoS medicine.

[43]  C. Palmer,et al.  An obesity-associated FTO gene variant and increased energy intake in children. , 2008, The New England journal of medicine.

[44]  H. Snieder,et al.  FTO variant rs9939609 is associated with body mass index and waist circumference, but not with energy intake or physical activity in European- and African-American youth , 2010, BMC Medical Genetics.

[45]  MJ Bond,et al.  The measurement of dietary restraint, disinhibition and hunger: an examination of the factor structure of the Three Factor Eating Questionnaire (TFEQ) , 2001, International Journal of Obesity.

[46]  M. Orho-Melander,et al.  Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity. , 2009, The American journal of clinical nutrition.

[47]  Fei Wang,et al.  The Fat Mass and Obesity Associated Gene FTO Functions in the Brain to Regulate Postnatal Growth in Mice , 2010, PloS one.

[48]  J. Després,et al.  Eating behaviors and indexes of body composition in men and women from the Québec family study. , 2003, Obesity research.

[49]  P. Elliott,et al.  Common genetic variation near MC4R is associated with eating behaviour patterns in European populations , 2009, International Journal of Obesity.

[50]  T. Lehtimäki,et al.  FTO genotype is associated with body mass index after the age of seven years but not with energy intake or leisure-time physical activity. , 2009, The Journal of clinical endocrinology and metabolism.

[51]  Roberta McKean-Cowdin,et al.  Genetic variants in association studies – review of strengths and weaknesses in study design and current knowledge of impact on cancer risk , 2009, Acta oncologica.

[52]  K. Rickels,et al.  A Comparison of Two Psychiatric Screening Tests , 1976, British Journal of Psychiatry.

[53]  M. Martínez-Larrad,et al.  The FTO Obesity Gene. Genotyping and Gene Expression Analysis in Morbidly Obese Patients , 2009, Obesity surgery.

[54]  T. Perneger What's wrong with Bonferroni adjustments , 1998, BMJ.

[55]  C. Carlberg,et al.  Carboxylic ester antagonists of 1α,25-dihydroxyvitamin D3 show cell-specific actions , 2000 .

[56]  Hongyu Zhao,et al.  FTO gene SNPs associated with extreme obesity in cases, controls and extremely discordant sister pairs , 2008, BMC Medical Genetics.

[57]  A. Astrup,et al.  Risk Factors for Adult Overweight and Obesity: The Importance of Looking Beyond the ‘Big Two’ , 2010, Obesity Facts.

[58]  A. Leong Diet, Nutrition, and the Prevention of Chronic Diseases , 1992 .

[59]  K. Pirke,et al.  A comparison of the validity of three scales for the assessment of dietary restraint. , 1989, Journal of abnormal psychology.

[60]  C. Davis,et al.  Psychobiological traits in the risk profile for overeating and weight gain , 2009, International Journal of Obesity.

[61]  A. Martí,et al.  Interaction between genes and lifestyle factors on obesity , 2008, Proceedings of the Nutrition Society.

[62]  N. Stefan,et al.  Variation in the FTO gene influences food intake but not energy expenditure. , 2008, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[63]  M. Rietschel,et al.  Depressive disorder moderates the effect of the FTO gene on body mass index , 2012, Molecular Psychiatry.

[64]  B. Ainsworth,et al.  Ability of the Atherosclerosis Risk in Communities (ARIC)/Baecke Questionnaire to assess leisure-time physical activity. , 1995, International journal of epidemiology.

[65]  Boyd Swinburn,et al.  Diet, nutrition and the prevention of chronic diseases. , 2003, World Health Organization technical report series.

[66]  J. Wardle,et al.  Obesity associated genetic variation in FTO is associated with diminished satiety. , 2008, The Journal of clinical endocrinology and metabolism.

[67]  Roger D. Cox,et al.  Overexpression of Fto leads to increased food intake and results in obesity , 2010, Nature Genetics.

[68]  T. Olds,et al.  Anthropometrica : a textbook of body measurement for sports and health courses , 1996 .

[69]  J E Frijters,et al.  A short questionnaire for the measurement of habitual physical activity in epidemiological studies. , 1982, The American journal of clinical nutrition.

[70]  G. Yeo,et al.  Where to go with FTO? , 2011, Trends in Endocrinology & Metabolism.

[71]  James Strait,et al.  Genome-Wide Association Scan Shows Genetic Variants in the FTO Gene Are Associated with Obesity-Related Traits , 2007, PLoS genetics.

[72]  T. Frayling,et al.  Piecing together the FTO jigsaw , 2011, Genome Biology.

[73]  D. J. Lee Society and the Adolescent Self-Image , 1969 .

[74]  L. Gauvin,et al.  Trying to lose weight: the association of income and age to weight-loss strategies in the U.S. , 2014, American journal of preventive medicine.

[75]  M. Westerterp-Plantenga,et al.  Predictors of long-term weight maintenance. , 2005, Obesity research.

[76]  R. Wing,et al.  Obesity susceptibility loci and dietary intake in the Look AHEAD Trial. , 2012, The American journal of clinical nutrition.

[77]  J. Speakman,et al.  Polymorphisms of the FTO Gene Are Associated With Variation in Energy Intake, but not Energy Expenditure , 2008, Obesity.

[78]  P S Freedson,et al.  Comparison of activity levels using the Caltrac accelerometer and five questionnaires. , 1994, Medicine and science in sports and exercise.

[79]  A. Stunkard,et al.  Validation of the flexible and rigid control dimensions of dietary restraint. , 1999, The International journal of eating disorders.

[80]  D. Nyholt A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. , 2004, American journal of human genetics.

[81]  R Core Team,et al.  R: A language and environment for statistical computing. , 2014 .

[82]  Jens C. Brüning,et al.  Inactivation of the Fto gene protects from obesity , 2009, Nature.

[83]  Chengqi Yi,et al.  N6-Methyladenosine in Nuclear RNA is a Major Substrate of the Obesity-Associated FTO , 2011, Nature chemical biology.

[84]  S. Yanovski,et al.  The FTO gene rs9939609 obesity-risk allele and loss of control over eating. , 2009, The American journal of clinical nutrition.