FTO genotype impacts food intake and corticolimbic activation
| Autor: | Mary K. Askren, Vidhi Tyagi, Susan J. Melhorn, Mary Rosalynn B. De Leon, Mario Kratz, Rudolph L. Leibel, Tyler A. Bosch, Wendy K. Chung, Thomas J. Grabowski, Mary F. Webb, Ellen A. Schur |
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| Rok vydání: | 2018 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine Calorie Genotyping Techniques Appetite Medicine (miscellaneous) FTO gene Body Mass Index 0302 clinical medicine Glucagon-Like Peptide 1 Surveys and Questionnaires media_common Meal Nutrition and Dietetics Brain Magnetic Resonance Imaging Ghrelin Ventral tegmental area Original Research Communications medicine.anatomical_structure Body Composition Female Adult medicine.medical_specialty Genotype media_common.quotation_subject Alpha-Ketoglutarate-Dependent Dioxygenase FTO 030209 endocrinology & metabolism Satiation Polymorphism Single Nucleotide Young Adult 03 medical and health sciences Internal medicine medicine Humans Obesity Alleles business.industry Ventral striatum medicine.disease Diet Cross-Sectional Studies 030104 developmental biology Endocrinology Lean body mass Energy Intake business |
| Zdroj: | The American Journal of Clinical Nutrition. 107:145-154 |
| ISSN: | 0002-9165 |
| DOI: | 10.1093/ajcn/nqx029 |
| Popis: | BACKGROUND: Variants in the first intron of the fat mass and obesity-associated (FTO) gene increase obesity risk. People with “high-risk” FTO genotypes exhibit preference for high-fat foods, reduced satiety responsiveness, and greater food intake consistent with impaired satiety. OBJECTIVE: We sought central nervous system mechanisms that might underlie impaired satiety perception in people with a higher risk of obesity based on their FTO genotype. DESIGN: We performed a cross-sectional study in a sample that was enriched for obesity and included 20 higher-risk participants with the AA (risk) genotype at the rs9939609 locus of FTO and 94 lower-risk participants with either the AT or TT genotype. We compared subjective appetite, appetite-regulating hormones, caloric intake at a buffet meal, and brain response to visual food cues in an extended satiety network using functional MRI scans acquired before and after a standardized meal. RESULTS: Higher-risk participants reported less subjective fullness (χ(2) = 7.48, P < 0.01), rated calorie-dense food as more appealing (χ(2) = 3.92, P < 0.05), and consumed ∼350 more kilocalories than lower-risk participants (β = 348 kcal, P = 0.03), even after adjusting for fat or lean mass. Premeal, the higher-risk group had greater activation by “fattening” food images (compared with objects) in the medial orbital frontal cortex (β = 11.6; 95% CI: 1.5, 21.7; P < 0.05). Postmeal, the higher-risk subjects had greater activation by fattening (compared with nonfattening) food cues in the ventral tegmental area/substantia nigra (β = 12.8; 95% CI: 2.7, 23.0; P < 0.05), amygdala (β = 10.6; 95% CI: 0.7, 20.5; P < 0.05), and ventral striatum (β = 6.9; 95% CI: 0.2, 13.7; P < 0.05). Moreover, postmeal activation by fattening food cues within the preselected extended satiety network was positively associated with energy intake at the buffet meal (R(2) = 0.29, P = 0.04) and this relation was particularly strong in the dorsal striatum (R(2) = 0.28, P = 0.01), amygdala (R(2) = 0.28, P = 0.03), and ventral tegmental area/substantia nigra (R(2) = 0.27, P = 0.01). CONCLUSION: The findings are consistent with a model in which allelic variants in FTO raise obesity risk through impaired central nervous system satiety processing, thereby increasing food intake. This study is registered at clinicaltrials.gov as NCT02483663. |
| Databáze: | OpenAIRE |
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