title: FTO genotype and aging: pleiotropic longitudinal effects on adiposity, brain function, impulsivity and diet.
abstract: Although overweight and obesity are associated with poor health outcomes in the elderly, the biological bases of obesity-related behaviors during aging are poorly understood. Common variants in the FTO gene are associated with adiposity in children and younger adults as well as with adverse mental health in older individuals. However, it is unclear whether FTO influences longitudinal trajectories of adiposity and other intermediate phenotypes relevant to mental health during aging. We examined whether a commonly carried obesity-risk variant in the FTO gene (rs1421085 single-nucleotide polymorphism) influences adiposity and is associated with changes in brain function in participants within the Baltimore Longitudinal Study of Aging, one of the longest-running longitudinal aging studies in the United States. Our results show that obesity-related risk allele carriers of FTO gene show dose-dependent increments in body mass index during aging. Moreover, the obesity-related risk allele is associated with reduced medial prefrontal cortical function during aging. Consistent with reduced brain function in regions intrinsic to impulse control and taste responsiveness, risk allele carriers of FTO exhibit dose-dependent increments in both impulsivity and intake of fatty foods. We propose that a common neural mechanism may underlie obesity-associated impulsivity and increased consumption of high-calorie foods during aging.
authors.affiliation: Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Y-F
authors.initials: YF
authors.lastname: Chuang
authors.affiliation: Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
authors.forename: T
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: L L
authors.initials: LL
authors.lastname: Beason-Held
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: An
authors.affiliation: College of Medicine, Florida State University, Tallahassee, FL, USA.
authors.forename: A
authors.initials: A
authors.lastname: Terracciano
authors.affiliation: College of Medicine, Florida State University, Tallahassee, FL, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Sutin
authors.affiliation: Department of Radiology, Johns Hopkins Medical Institutions, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Kraut
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, Baltimore, MD, USA.
authors.forename: A B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Resnick
authors.affiliation: Clinical and Translational Neuroscience Unit, Laboratory of Behavioral Neuroscience, National Institute on Aging, Baltimore, MD, USA.
authors.forename: M
authors.initials: M
authors.lastname: Thambisetty
mesh_terms: D050154:Adiposity / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D001921:Brain / Q000000981:diagnostic imaging; D004032:Diet; D004435:Eating / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D011877:Radionuclide Imaging; D014481:United States; D055815:Young Adult
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human