The prevalence of obesity and its attendant co-morbidities are increasing at the rate of approximately 20% per decade in adults and children. The salient phenotypes (primarily increased energy intake) that promote weight gain are more evident during- than after- weight gain. Therefore, analyses of the mechanisms leading to weight gain are more likely to be illuminating in studies of children who are 'at high vs. low risk of becoming obese adults as opposed to studies of adults who are already overweight compared to lean subjects. An extremely common (allelic frequency of ~40%) SNP at the FTO locus (rs9939609) that is associated with early onset obesity and increased food intake in experimental settings has recently been identified. In addition, recent studies document that: 1) Changes in eating behavior can be detected in structured, objective meal paradigms among children with allelic variants that place them 'at risk' for obesity, but who are not yet obese. Th central hypotheses of these studies are: 1) Energy intake and mean energy density of selected foods are increased in children with one (AT) or two (AA) copies of the rs9939609 obesity-risk (A) SNP of FTO/FTM compared to those who are unaffected (TT), 2) Using functional magnetic resonance imaging (fMRI), affected children (AA or AT) will demonstrate enhanced ventral frontostriatal responses to food stimuli and/or reduced inhibitory input from prefrontal centers compared to those without it, showing a dose response of the at-risk allele (AA>AT>TT). Over 5 years we plan to study 30 'trios' consisting of gender-, age-, and weight-matched 6-9 year olds (1 AA, 1 AT, and 1 TT). These studies are unique in examining eating behavior and the functioning of relevant CNS circuits among individuals at varying degrees of risk for obesity who, at the time of study, will be 'pre-obese', thus avoiding the confounds of obesity per se on these behavioral and imaging phenotypes.
The prevalence of obesity and its attendant co-morbidities are increasing at the alarming rate of approximately 20% per decade in adults and children. The mechanisms leading to weight gain are more likely to be illuminated in studies of children who are at risk of becoming obese adults as opposed to studies of adults who are already overweight. Advancing our understanding of the neurocircuitry subserving the development of obesity is an essential step in developing new prevention and treatment strategies for this public health priority.
|Teslovich, Theresa; Freidl, Eve K; Kostro, Katrina et al. (2014) Probing behavioral responses to food: development of a food-specific go/no-go task. Psychiatry Res 219:166-70|