The high prevalence of childhood obesity in the U.S. demands a better understanding of factors that drive weight gain and influence the outcome of pediatric obesity interventions. This project investigates the hypothesis that, as in adults, a subset of obese children experience a diminished satiety response to food consumption, and that these children are more resistant to gold standard family-based behavioral treatment (FBT) for obesity. FBT is targeted almost exclusively toward parents;however, there is evidence that obesity development and response to intervention may depend on additional factors such as individual internal satiety perception and variability in the function of brain centers associated with impulsivity and reward. The proposed research uses functional magnetic resonance imaging (fMRI) to characterize brain function related to satiety and examines fMRI along with behavioral, cognitive, and hormonal testing to fully examine potential mediators of children's experience of satiety and response to FBT. The approach is based on evidence that failure to attenuate the reward value of palatable foods after eating can be a manifestation of a blunted central satiety response that is reliably detected using fMRI. Key objectives will be to determine if differences in the central satiety response exist between obese and non-obese children, and, among obese children, if the strength of the central satiety response is associated with impulsivity and/or the success of obesity treatment. The central hypothesis is that, in obese children, a blunted central nervous system satiety response impairs the success of obesity interventions. To achieve study objectives, brain activation by high-calorie visual food cues before and after food consumption will be measured by fMRI. Participants will be obese and non-obese children aged 9-11 years. The 49 obese children will be evaluated before and after they participate in a 6-month evidence-based FBT intervention. Their pre-intervention fMRI will be compared to those of 20 non-obese controls to test for a blunted central satiety response (Aim 1). The relationship of impulsivity to satiety responses and food intake will be determined in obese children (Aim 2). The longitudinal component tests whether central satiety responses prior to treatment predict treatment outcomes (Aim 3A) and whether changes in central satiety responses during treatment predict maintenance of reduced weight 6 and 12 months after treatment cessation (Aim 3B). Behavioral, cognitive, and hormonal measures will be examined as potential mediating or confounding factors contributing to fMRI responses. The proposed research is guided by an integrated, transdisciplinary team with expertise in pediatric and adult neuroimaging, appetite regulation, and family-based childhood obesity treatment. This research will provide new insights into the neurobiological basis of child obesity and the relevance of neurobiological factors to treatment success. The long-term objective is to translate these findings to improve obesity interventions cost-effectively and sustain better long-term results.
The proposed study examines brain activation in obese children in response to food images before and after obesity intervention. Using functional neuroimaging, this study will test a new theory that some obese children's success in treatment is undermined if their response to high-calorie food images is not suppressed in reward centers of the brain following food intake. Based on the results, future studies will refine treatment procedures, developing and testing alternate strategies for childhood obesity treatment.
|Berkseth, Kathryn E; Rubinow, Katya B; Melhorn, Susan J et al. (2018) Hypothalamic Gliosis by MRI and Visceral Fat Mass Negatively Correlate with Plasma Testosterone Concentrations in Healthy Men. Obesity (Silver Spring) 26:1898-1904|
|Chepurny, Oleg G; Bonaccorso, Ron L; Leech, Colin A et al. (2018) Chimeric peptide EP45 as a dual agonist at GLP-1 and NPY2R receptors. Sci Rep 8:3749|
|Schur, Ellen; Carnell, Susan (2017) What Twin Studies Tell Us About Brain Responses to Food Cues. Curr Obes Rep 6:371-379|
|Roth, Christian L; D'Ambrosio, Gabrielle; Elfers, Clinton (2016) Activation of nuclear factor kappa B pathway and reduction of hypothalamic oxytocin following hypothalamic lesions. J Syst Integr Neurosci 2:79-84|
|Mestre, Zoe Lucille; Melhorn, Susan J; Askren, Mary K et al. (2016) Effects of Anxiety on Caloric Intake and Satiety-Related Brain Activation in Women and Men. Psychosom Med 78:454-64|
|Melhorn, Susan J; Mehta, Sonya; Kratz, Mario et al. (2016) Brain regulation of appetite in twins. Am J Clin Nutr 103:314-22|