TY - JOUR
T1 - Association between the FTO rs9939609 single nucleotide polymorphism and dietary adherence during a 2-year caloric restriction intervention
T2 - Exploratory analyses from CALERIE™ phase 2
AU - Dorling, James L.
AU - Belsky, Daniel W.
AU - Racette, Susan B.
AU - Das, Sai Krupa
AU - Ravussin, Eric
AU - Redman, Leanne M.
AU - Höchsmann, Christoph
AU - Huffman, Kim M.
AU - Kraus, William E.
AU - Kobor, Michael S.
AU - MacIsaac, Julia L.
AU - Lin, David T.S.
AU - Corcoran, David L.
AU - Martin, Corby K.
N1 - Funding Information:
The research was supported by the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (grants U01AG022132, U01AG020478, U01AG020487, U01AG020480, R01-AG061378, and R33-AG070455); Nutrition Obesity Research Center (grant P30 DK072476), sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases; and the National Institute of General Medical Sciences of the National Institutes of Health, which funds the Louisiana Clinical and Translational Science Center (grant 1 U54 GM104940). Further, the work was supported by the American Heart Association (grant #20POST35210907) (J.L.D), and C. H is supported by a National Institutes of Health National Research Service Award (T32 DK064584). D.W.B and M.K. are fellows of the Canadian Institute for Advanced Research Child Brain Development Network. The funder for this analysis had a role in study design and data collection but had no role in data analysis, data interpretation, writing of the manuscript, or decision to submit the manuscript.
Funding Information:
The research was supported by the National Institute on Aging and the National Institute of Diabetes and Digestive and Kidney Diseases , National Institutes of Health (grants U01AG022132 , U01AG020478 , U01AG020487 , U01AG020480 , R01-AG061378 , and R33-AG070455 ); Nutrition Obesity Research Center (grant P30 DK072476 ), sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases ; and the National Institute of General Medical Sciences of the National Institutes of Health , which funds the Louisiana Clinical and Translational Science Center (grant 1 U54 GM104940 ). Further, the work was supported by the American Heart Association (grant # 20POST35210907 ) (J.L.D), and C. H is supported by a National Institutes of Health National Research Service Award ( T32 DK064584 ). D.W.B and M.K. are fellows of the Canadian Institute for Advanced Research Child Brain Development Network. The funder for this analysis had a role in study design and data collection but had no role in data analysis, data interpretation, writing of the manuscript, or decision to submit the manuscript.
Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/11
Y1 - 2021/11
N2 - 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/m2) 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.
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/m2) 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.
KW - Aging
KW - Eating behaviors
KW - Fat mass and obesity-associated gene
KW - Longevity
KW - Metabolic adaptation
KW - Personalized nutrition
UR - http://www.scopus.com/inward/record.url?scp=85115984522&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2021.111555
DO - 10.1016/j.exger.2021.111555
M3 - Article
C2 - 34543722
AN - SCOPUS:85115984522
SN - 0531-5565
VL - 155
JO - Experimental Gerontology
JF - Experimental Gerontology
M1 - 111555
ER -