PMID- 34543722 OWN - NLM STAT- MEDLINE DCOM- 20211213 LR - 20221102 IS - 1873-6815 (Electronic) IS - 0531-5565 (Print) IS - 0531-5565 (Linking) VI - 155 DP - 2021 Nov TI - Association between the FTO rs9939609 single nucleotide polymorphism and dietary adherence during a 2-year caloric restriction intervention: Exploratory analyses from CALERIE phase 2. PG - 111555 LID - S0531-5565(21)00337-5 [pii] LID - 10.1016/j.exger.2021.111555 [doi] AB - Caloric restriction (CR) improves markers of aging in humans; but it is not known if the fat mass and obesity-associated gene (FTO) rs9939609 single nucleotide polymorphism (SNP), which is associated with appetite and energy intake, influences adherence to prolonged CR. Utilizing data from the two-year Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) phase 2 randomized controlled trial, we tested whether the FTO rs9939609 SNP was associated with adherence to CR in healthy adults without obesity. As secondary aims, we assessed whether the FTO rs9939609 SNP was associated with changes in body composition, biomarkers of aging, and eating behaviors. Participants were randomized into either a CR group that targeted a 25% reduction in energy intake compared to the habitual energy intake at baseline, or an ad libitum (AL) control group. Participants were genotyped for the FTO rs9939609 SNP. Dietary adherence was determined through changes in energy intake using doubly labeled water and changes in body composition at baseline, month 12, and month 24 in both the CR and AL condition. Weight, body composition, resting metabolic rate (RMR), adiponectin, insulin, leptin, and eating behaviors were measured at the same timepoints. A total of 144 participants (91 CR and 53 AL, age: 38.6 +/- 7.1 years; body mass index: 25.3 +/- 1.7 kg/m(2)) were studied. Of these, 27 were homozygous for the 'obesity-risk' A allele (AA), while 44 were homozygous for the T allele (TT) and 73 were heterozygotes (AT). By design, the CR group exhibited greater percent CR compared to the AL group during the trial (P < 0.01), but no genotype-by-treatment interaction was observed for change in energy intake or percent CR (P >/= 0.40). The FTO rs9939609 SNP was also negligibly associated with change in most other endpoints (P >/= 0.13), though AAs showed a reduction in RMR adjusted for body composition change over the 24 months relative to TTs (genotype-by-treatment interaction: P = 0.03). In a two-year CR intervention delivered to healthy individuals without obesity, the FTO rs9939609 SNP was not associated with adherence to CR and did not alter improvements in most aging biomarkers. CI - Copyright (c) 2021 Elsevier Inc. All rights reserved. FAU - Dorling, James L AU - Dorling JL AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA; Human Nutrition, School of Medicine, Dentistry and Nursing, College of Medical, Veterinary and Life of Sciences, University of Glasgow, UK(1). Electronic address: james.dorling@glasgow.ac.uk. FAU - Belsky, Daniel W AU - Belsky DW AD - Columbia University Mailman School of Public Health, New York, NY, USA. FAU - Racette, Susan B AU - Racette SB AD - Program in Physical Therapy and Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA. FAU - Das, Sai Krupa AU - Das SK AD - Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA, USA. FAU - Ravussin, Eric AU - Ravussin E AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA. FAU - Redman, Leanne M AU - Redman LM AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA. FAU - Hochsmann, Christoph AU - Hochsmann C AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA. FAU - Huffman, Kim M AU - Huffman KM AD - Duke University School of Medicine, Durham, NC, USA. FAU - Kraus, William E AU - Kraus WE AD - Duke University School of Medicine, Durham, NC, USA. FAU - Kobor, Michael S AU - Kobor MS AD - Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada. FAU - MacIsaac, Julia L AU - MacIsaac JL AD - Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada. FAU - Lin, David T S AU - Lin DTS AD - Centre for Molecular Medicine and Therapeutics, BC Children's Hospital Research Institute, University of British Columbia, Vancouver, Canada. FAU - Corcoran, David L AU - Corcoran DL AD - Duke Center for Genomic and Computational Biology, Duke University, Durham, NC, USA. FAU - Martin, Corby K AU - Martin CK AD - Pennington Biomedical Research Center, Baton Rouge, LA, USA. LA - eng GR - R33 AG070455/AG/NIA NIH HHS/United States GR - U01 AG020487/AG/NIA NIH HHS/United States GR - U01 AG020478/AG/NIA NIH HHS/United States GR - U01 AG020480/AG/NIA NIH HHS/United States GR - P30 DK072476/DK/NIDDK NIH HHS/United States GR - U54 GM104940/GM/NIGMS NIH HHS/United States GR - U01 AG022132/AG/NIA NIH HHS/United States GR - R01 AG061378/AG/NIA NIH HHS/United States GR - P30 DK056341/DK/NIDDK NIH HHS/United States GR - T32 DK064584/DK/NIDDK NIH HHS/United States PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20210920 PL - England TA - Exp Gerontol JT - Experimental gerontology JID - 0047061 RN - EC 1.14.11.33 (Alpha-Ketoglutarate-Dependent Dioxygenase FTO) RN - EC 1.14.11.33 (FTO protein, human) SB - IM MH - Alpha-Ketoglutarate-Dependent Dioxygenase FTO/genetics MH - Body Mass Index MH - *Caloric Restriction MH - Energy Intake MH - Genetic Predisposition to Disease MH - Genotype MH - Humans MH - *Polymorphism, Single Nucleotide PMC - PMC8720865 MID - NIHMS1762921 OTO - NOTNLM OT - Aging OT - Eating behaviors OT - Fat mass and obesity-associated gene OT - Longevity OT - Metabolic adaptation OT - Personalized nutrition COIS- DECLARATION OF INTEREST: None. EDAT- 2021/09/21 06:00 MHDA- 2021/12/15 06:00 PMCR- 2022/11/01 CRDT- 2021/09/20 20:14 PHST- 2021/06/16 00:00 [received] PHST- 2021/08/20 00:00 [revised] PHST- 2021/09/09 00:00 [accepted] PHST- 2021/09/21 06:00 [pubmed] PHST- 2021/12/15 06:00 [medline] PHST- 2021/09/20 20:14 [entrez] PHST- 2022/11/01 00:00 [pmc-release] AID - S0531-5565(21)00337-5 [pii] AID - 10.1016/j.exger.2021.111555 [doi] PST - ppublish SO - Exp Gerontol. 2021 Nov;155:111555. doi: 10.1016/j.exger.2021.111555. Epub 2021 Sep 20.