{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T14:24:18Z","timestamp":1772115858396,"version":"3.50.1"},"reference-count":37,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T00:00:00Z","timestamp":1571356800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The rs9939609 polymorphism of the fat mass and obesity-associated (FTO) gene has been associated with obesity, and studies have also shown that environmental\/lifestyle interaction such as dietary intake might mediate this effect. The current study investigates the postprandial hormonal regulators of hunger and indirect markers of substrate utilisation and metabolic flexibility following a dietary challenge to determine if suppression of circulating ghrelin levels and\/or reduced metabolic flexibility exist between FTO genotypes. One hundred and forty seven healthy, sedentary males and females (29.0 \u00b1 0.7 yrs; 70.2 \u00b1 1.1 kg; 169.1 \u00b1 0.8 cm; 24.5 \u00b1 0.3 kg\/m2) complete a single experimental session. Anthropometric measures, circulating levels of active ghrelin, insulin and glucose, and substrate oxidation via indirect calorimetry, are measured pre-prandial and\/or post-prandial. The FTO rs9939609 variant is genotyped using a real-time polymerase chain reaction. Metabolic flexibility (\u2206RER) is similar between FTO genotypes of the rs9939609 (T &gt; A) polymorphism (p &gt; 0.05). No differences in pre-prandial and\/or postprandial substrate oxidation, plasma glucose, serum insulin or ghrelin are observed between genotypes (p &gt; 0.05). These observations are independent of body mass index and gender. Altered postprandial responses in hunger hormones and metabolic flexibility may not be a mechanism by which FTO is associated with higher BMI and obesity in healthy, normal-weighted individuals.<\/jats:p>","DOI":"10.3390\/nu11102518","type":"journal-article","created":{"date-parts":[[2019,10,18]],"date-time":"2019-10-18T11:24:15Z","timestamp":1571397855000},"page":"2518","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Similarities in Metabolic Flexibility and Hunger Hormone Ghrelin Exist between FTO Gene Variants in Response to an Acute Dietary Challenge"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0201-003X","authenticated-orcid":false,"given":"Jessica","family":"Danaher","sequence":"first","affiliation":[{"name":"School of Science, College of Science, Engineering and Health, Royal Melbourne Institute of Technology (RMIT) University, Melbourne VIC 3083, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christos G.","family":"Stathis","sequence":"additional","affiliation":[{"name":"Institute for Health and Sport, Victoria University, Melbourne VIC 3011, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4978-4294","authenticated-orcid":false,"given":"Matthew B.","family":"Cooke","sequence":"additional","affiliation":[{"name":"Department of Health and Medical Sciences, Faculty of Health, Arts and Design, Swinburne University of Technology, Melbourne VIC 3122, Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS), Western Health, Melbourne VIC 3021, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1038\/sj.ijo.0801358","article-title":"Intrapair resemblance in very low calorie diet-induced weight loss in female obese identical twins","volume":"24","author":"Hainer","year":"2000","journal-title":"Int. J. Obes. Relat. Metab. Disord."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1023\/A:1025635913927","article-title":"Genetic and environmental factors in relative body weight and human obesity","volume":"27","author":"Maes","year":"1997","journal-title":"Behav. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1126\/science.1141634","article-title":"A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity","volume":"316","author":"Frayling","year":"2007","journal-title":"Science"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Le\u00f3n-Mimila, P., Villamil-Ram\u00edrez, H., Villalobos-Compar\u00e1n, M., Villarreal-Molina, T., Romero-Hidalgo, S., L\u00f3pez-Contreras, B., Guti\u00e9rrez-Vidal, R., Vega-Badillo, J., Jacobo-Albavera, L., and Posadas-Romeros, C. (2013). Contribution of common genetic variants to obesity and obesity-related traits in mexican children and adults. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070640"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.3945\/ajcn.111.026955","article-title":"Obesity susceptibility loci and dietary intake in the look ahead trial","volume":"95","author":"McCaffery","year":"2012","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1961","DOI":"10.1038\/oby.2008.318","article-title":"Polymorphisms of the FTO gene are associated with variation in energy intake, but not energy expenditure","volume":"16","author":"Speakman","year":"2008","journal-title":"Obesity"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1483","DOI":"10.3945\/ajcn.2009.28439","article-title":"The FTO gene rs9939609 obesity-risk allele and loss of control over eating","volume":"90","author":"Han","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3640","DOI":"10.1210\/jc.2008-0472","article-title":"Obesity associated genetic variation in FTO is associated with diminished satiety","volume":"93","author":"Wardle","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1038\/ng.713","article-title":"Overexpression of Fto leads to increased food intake and results in obesity","volume":"42","author":"Church","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"199","DOI":"10.2147\/DMSO.S154978","article-title":"Influence of FTO rs9939609 polymorphism on appetite, ghrelin, leptin, IL6, TNF\u03b1 levels, and food intake of women with morbid obesity","volume":"11","author":"Magno","year":"2018","journal-title":"Diabetes Metab. Syndr. Obes."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3539","DOI":"10.1172\/JCI44403","article-title":"A link between FTO, ghrelin, and impaired brain food-cue responsivity","volume":"123","author":"Karra","year":"2013","journal-title":"J. Clin. Investig."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1038\/ijo.2017.123","article-title":"Butyrylcholinesterase regulates central ghrelin signaling and has an impact on food intake and glucose homeostasis","volume":"41","author":"Chen","year":"2017","journal-title":"Int. J. Obes."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Dorling, J.L., Clayton, D.J., Jones, J., Carter, W., Thackray, A.E., King, J.A., Pucci, A., Batterham, R.L., and Stensel, D.J. (2019). A randomized cross-over trial assessing the effects of acute exercise on appetite, circulating ghrelin concentrations and butyrylcholinesterase activity in normal weight males with variants of the obesity-linked FTO rs9939609 polymorphism. Am. J. Clin. Nutr., in press.","DOI":"10.1093\/ajcn\/nqz188"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/ajcn\/nqx029","article-title":"FTO genotype impacts food intake and corticolimbic activation","volume":"107","author":"Melhorn","year":"2018","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1016\/j.cmet.2017.04.015","article-title":"Metabolic flexibility in health and disease","volume":"25","author":"Goodpaster","year":"2017","journal-title":"Cell Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2402","DOI":"10.2337\/db09-0205","article-title":"Regulation and function of FTO mRNA expression in human skeletal muscle and subcutaneous adipose tissue","volume":"58","author":"Grunnet","year":"2009","journal-title":"Diabetes"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"258","DOI":"10.2337\/db10-0281","article-title":"FTO is increased in muscle during type 2 diabetes, and its overexpression in myotubes alters insulin signaling, enhances lipogenesis and ROS production, and induces mitochondrial dysfunction","volume":"60","author":"Bravard","year":"2011","journal-title":"Diabetes"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e41606","DOI":"10.1038\/srep41606","article-title":"AMPK regulates lipid accumulation in skeletal muscle cells through FTO-dependent demethylation of N6-methyladenosine","volume":"4","author":"Wu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1462","DOI":"10.2337\/diacare.22.9.1462","article-title":"Insulin sensitivity indices obtained from oral glucose tolerance testing: Comparison with the euglycemic insulin clamp","volume":"22","author":"Matsuda","year":"1999","journal-title":"Diabetes Care"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"412","DOI":"10.1007\/BF00280883","article-title":"Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man","volume":"28","author":"Matthews","year":"1985","journal-title":"Diabetologia"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1055\/s-2004-830512","article-title":"Measurement of substrate oxidation during exercise by means of gas exchange measurements","volume":"26","author":"Jeukendrup","year":"2005","journal-title":"Int. J. Sports Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"205","DOI":"10.3389\/fncel.2019.00205","article-title":"The role of ghrelin in regulating synaptic function and plasticity of feeding-associated circuits","volume":"13","author":"Serrenho","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1093\/jn\/nxz062","article-title":"True interindividual variability exists in postprandial appetite responses in healthy men but is not moderated by the FTO genotype","volume":"149","author":"Goltz","year":"2019","journal-title":"J. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"20028","DOI":"10.3402\/fnr.v57i0.20028","article-title":"Genetic variation in the fat mass and obesity-associated gene (FTO) in association with food preferences in healthy adults","volume":"57","author":"Brunkwall","year":"2013","journal-title":"Food Nutr. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1418","DOI":"10.3945\/ajcn.2009.27958","article-title":"Fat and carbohydrate intake modify the association between genetic variation in the FTO genotype and obesity","volume":"90","author":"Sonestedt","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1210\/jc.2008-1199","article-title":"FTO genotype is associated with body mass index after the age of seven years but not with energy intake of leisure-time physical activity","volume":"94","author":"Hakanen","year":"2009","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Liu, G., Zhu, H., Lagou, V., Gutin, B., Stallmann-Jorgensen, I.S., Treiber, F.A., Dong, Y., and Snieder, H. (2010). 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. BMC Med. Genet., 11.","DOI":"10.1186\/1471-2350-11-57"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1555","DOI":"10.1093\/ajcn\/nqz017","article-title":"The effect of high compared with low dairy consumption on glucose metabolism, insulin sensitivity, and metabolic flexibility in overweight adults: A randomized crossover trial","volume":"109","author":"Eelderink","year":"2019","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1039\/c1fo10133a","article-title":"The importance of the long-chain polyunsaturated fatty acid n-6\/n-3 ratio in development of non-alcoholic fatty liver associated with obesity","volume":"2","author":"Valenzuela","year":"2011","journal-title":"Food Funct."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.plefa.2016.10.001","article-title":"Long-chain polyunsaturated fatty acids regulation of PPARs, signaling: Relationship to tissue development and aging","volume":"114","author":"Ortiz","year":"2016","journal-title":"Prostaglandins Leukot Essent Fat. Acids"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Pitman, R.T., Fong, J.T., Billman, P., and Puri, N. (2012). Knockdown of the fat mass and obesity gene disrupts cellular energy balance in a cell-type specific manner. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038444"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"2904","DOI":"10.1210\/jc.2008-0007","article-title":"Lack of association of fatness-related FTO gene variants with energy expenditure or physical activity","volume":"93","author":"Berentzen","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2558","DOI":"10.1056\/NEJMoa0803839","article-title":"An obesity-associated FTO gene variant and increased energy intake in children","volume":"359","author":"Cecil","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/oby.2008.24","article-title":"Impaired skeletal muscle substrate oxidation in glucose-intolerant men improves after weight loss","volume":"16","author":"Corpeleijn","year":"2008","journal-title":"Obesity"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"957","DOI":"10.2337\/diacare.31.11.957","article-title":"The effect of graded doses of insulin on total glucose uptake, glucose oxidation, and glucose storage in man","volume":"31","author":"Thiebaud","year":"1982","journal-title":"Diabetes"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1111\/j.1365-2036.2011.04609.x","article-title":"Review article: The role of gastric motility in the control of food intake","volume":"33","author":"Janseen","year":"2011","journal-title":"Aliment. Pharm. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1172\/JCI25758","article-title":"Skeletal muscle fat oxidation: Timing and flexibility are everything","volume":"115","author":"Kelley","year":"2005","journal-title":"J. Clin. Investig."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/10\/2518\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:27:39Z","timestamp":1760189259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/11\/10\/2518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,18]]},"references-count":37,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10]]}},"alternative-id":["nu11102518"],"URL":"https:\/\/doi.org\/10.3390\/nu11102518","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,18]]}}}