Association between the FTO rs9939609 single nucleotide polymorphism and dietary adherence during a 2-year caloric restriction intervention: Exploratory analyses from CALERIE™ phase 2

• Published in: Experimental gerontology 2021-11, Vol.155, p.111555-111555, Article 111555
• Main Authors: Dorling, James L., Belsky, Daniel W., Racette, Susan B., Das, Sai Krupa, Ravussin, Eric, Redman, Leanne M., Höchsmann, Christoph, Huffman, Kim M., Kraus, William E., Kobor, Michael S., MacIsaac, Julia L., Lin, David T.S., Corcoran, David L., Martin, Corby K.
• Format: Article
• Language: English
• Subjects: Aging; Alpha-Ketoglutarate-Dependent Dioxygenase FTO - genetics; Body Mass Index; Caloric Restriction; Eating behaviors; Energy Intake; Fat mass and obesity-associated gene; Genetic Predisposition to Disease; Genotype; Humans; Longevity; Metabolic adaptation; Personalized nutrition; Polymorphism, Single Nucleotide
• ISSN: 0531-5565; 1873-6815
• DOI: 10.1016/j.exger.2021.111555

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