Family-based behavioral treatment (FBT) is the recommended intervention for children with obesity (OB). However, there is a large variability in short- and long-term treatment response and mechanisms for unsuccessful treatment outcomes are not understood. We studied brain regions involved in satiety processing in 9-11-year-old children with obesity (OB, n=54) and children with healthy weight (HW, n=22). Subjects underwent a functional magnetic resonance imaging scan to examine response to visual food cues followed by a test meal and then a second scan. In OB children, neuroimaging procedures were repeated after ending 6-months of FBT. Mean extracted neural activation for the contrasts of high- and low-calorie food cues vs. objects were assessed across a priori brain regions of interest: ventral and dorsal striatum, amygdala, ventral tegmental area/substantia nigra, insula and medial orbitofrontal cortex. Forty OB subjects completed FBT. At the end of FBT, 55% of OB children showed clinically significant reductions in BMI z-score of -0.125 or more. However, even after successful treatment, over two-thirds of children increased their BMI z-score 6-12 months after ending FBT. FBT responders reduced their leptin (mean) from 32.9 to 18.9 ng/ml (P<0.0001), potentially contributing to subsequent weight regain, while in non-responders leptin increased from 33.8 to 37.6 ng/ml. At baseline pre-FBT, OB vs. HW children exhibited an attenuated average central response to a satiating meal in which they did not reduce activation by high-calorie food cues across the a priori regions (P<0.01). Among OB subjects greater pre-treatment extent of pre- to post-meal reduction of neural activation by high-calorie food cues (i.e., similar to the response of HW children) predicted better BMI z-score reduction at the end of FBT (P=0.03). However, a stronger BMI z-score reduction in FBT was associated with a worsened brain satiety response after treatment (P=0.03), potentially predisposing, even children who were initially responsive to FBT, to increased subsequent motivation to eat and weight regain. These findings implicate an attenuated central satiety response in OB vs. HW children and that the brain's response to a meal can predict FBT treatment outcomes in OB children. An impaired central satiety response can be a barrier to immediate and sustained FBT treatment success. Clinicaltrials.gov #NCT02484976. Supported by R01DK098466 (CLR); R01DK089036 (EAS), and P30DK035816 (University of Washington Nutrition and Obesity Research Center).
19 - 21 Sep 2019
European Society for Paediatric Endocrinology