# Brain systems and behaviors underlying response to obesity treatment in children

> **NIH NIH R01** · SEATTLE CHILDREN'S HOSPITAL · 2020 · $680,326

## Abstract

PROJECT SUMMARY
 Given the high prevalence of childhood obesity in the U.S. and the lack of durable weight loss with
existing obesity interventions, new options that improve pediatric weight management are needed. Intensive
family-based behavioral treatment (FBT) is the gold-standard intervention for children with obesity and is
focused on changing food environments and parenting around children's eating. The proposed research is a
renewal of the Brain Activation and Satiety In Children (BASIC) study which used functional Magnetic
Resonance Imaging (fMRI) to better understand if neurobiological factors impact success in FBT. In this study,
55% of children with obesity treated with FBT showed clinically significant reductions in BMI z-score, and even
after successful treatment, over two-thirds of children increased their BMI z-score 6−12 months after ending
FBT. At baseline pre-FBT, children with obesity, compared to children of healthy weight, exhibited an
attenuated central response to a satiating meal in which they did not reduce activation by high-calorie food
cues across a set of a priori appetite-regulating brain regions. This pattern also was associated with worse FBT
outcomes among obese children undergoing FBT, specifically, less reduction in BMI z-score during treatment.
Further, greater BMI z-score reduction during FBT was associated with a decreased neural satiety response
after treatment. These findings implicate neurobiological factors as a negative input onto children's ability to
achieve and maintain clinically significant improvement in weight status via FBT. The proposed follow-up
project builds upon these findings and investigates the hypothesis that adding a glucagon-like peptide-1
receptor agonist (GLP-1RA) once weekly drug intervention to FBT will augment BMI z-score reduction, even
among children who seem initially resistant to FBT, by promoting greater reductions in neural activation in
response to a meal. In a double-blinded randomized placebo-controlled clinical trial among 64 children aged
10-12 years old, Specific Aim 1 will test the effect of adding GLP-1RA to FBT on change in BMI z-score over a
total GLP-1RA treatment duration of 24 weeks and a subsequent 1-year observational follow-up period after
treatment cessation. To provide mechanistic insight, Specific Aim 2 will test whether adding GLP-1RA
intervention to FBT impacts neural activation by food cues. Finally, the proposed research will investigate the
role of a cellular inflammatory process in the mediobasal hypothalamus ─called gliosis─ which might contribute
to impaired hypothalamic function, attenuated satiety responsiveness, and potentially to worse weight
management outcomes. Specific Aim 3 will test if hypothalamic gliosis is modified by FBT and/or FBT plus
GLP-1RA in children and if reduction of gliosis is associated with better long-term outcomes. This research
builds upon the team's prior findings to test a pharmacologic intervention with potential to m...

## Key facts

- **NIH application ID:** 10016236
- **Project number:** 5R01DK098466-06
- **Recipient organization:** SEATTLE CHILDREN'S HOSPITAL
- **Principal Investigator:** Christian Ludwig Roth
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $680,326
- **Award type:** 5
- **Project period:** 2014-09-01 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10016236

## Citation

> US National Institutes of Health, RePORTER application 10016236, Brain systems and behaviors underlying response to obesity treatment in children (5R01DK098466-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10016236. Licensed CC0.

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