Altered Hypothalamic functional connectivity in adolescents with severe obesity
Allison Shapiro1, Meghan Pauley1, Jaime M Moore2
1University of Colorado Anschutz.
Research Square
|February 12, 2026
Summary
Adolescents with severe obesity show altered brain connectivity between the hypothalamus and other regions in both fasting and fed states. This highlights the need to consider homeostatic brain circuits in pediatric obesity treatment.
Area of Science:
- Neuroscience
- Pediatric Obesity Research
- Brain Imaging
Background:
- Existing neurobiological models of youth obesity primarily focus on non-homeostatic systems.
- The homeostatic system, particularly the hypothalamus, is understudied in adolescent obesity.
- Understanding hypothalamic function is crucial for developing effective obesity treatments in adolescents.
Purpose of the Study:
- To investigate differences in hypothalamic functional connectivity in adolescents with severe obesity compared to healthy-weight peers.
- To examine these connectivity patterns across both fasting and fed states.
- To inform neurobiological frameworks of pediatric obesity.
Main Methods:
- Analysis of resting-state functional magnetic resonance imaging (fMRI) data from a randomized crossover trial.
- Comparison of functional connectivity originating from the hypothalamus between severe obesity (SO) and healthy weight (HW) adolescent groups.
- fMRI scans were acquired during fasting and after glucose ingestion, with statistical models adjusted for age and sex.
Main Results:
- During fasting, adolescents with SO showed weaker hypothalamic connectivity to the cerebellum and occipital gyrus, and stronger connectivity to the postcentral/supramarginal gyri compared to HW peers.
- In the fed state, SO adolescents exhibited altered hypothalamic connectivity, with increased connections to the middle frontal gyri and putamen, and decreased connections to the caudate and superior frontal gyrus.
- These alterations in connectivity were observed across both physiological states.
Conclusions:
- Severe obesity in adolescents is linked to disrupted communication between the homeostatic hypothalamus and non-homeostatic brain regions.
- Altered hypothalamic connectivity patterns persist across fasting and fed states in adolescents with severe obesity.
- Findings emphasize the importance of integrating homeostatic circuitry into neurobiological models for pediatric obesity.
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