# Impact of hypothalamic gliosis on appetite regulation and obesity risk in children

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2021 · $720,978

## Abstract

ABSTRACT
 Pediatric obesity is a harbinger of lifelong excess weight, suggesting that neurobiological processes
beginning in childhood could ultimately raise the defended level of body adiposity. Recent findings from rodent
models suggest a possible mechanism for this process: an inflammatory glial cell response—called gliosis—
occurs in the arcuate nucleus, plays a pathogenic role in diet-induced obesity, and involves neuronal loss and
potentially permanent glial scarring. The arcuate nucleus is located in the mediobasal hypothalamus (MBH)
and is the primary hypothalamic region regulating energy homeostasis; thus, neuronal damage or tissue
remodeling in this brain area could significantly impact regulation of body weight and appetite. Importantly,
gliosis is detectable in brain tissue in humans by magnetic resonance imaging (MRI). Using MRI, the
investigators discovered the first evidence of MBH gliosis in obese adults. The investigators' new findings show
that gliosis negatively impacts brain regulation of appetite in adults and that MBH gliosis is also present in
children with greater adiposity. Our overarching hypothesis is that the presence of MBH gliosis contributes to
reduced satiety responsiveness and poor intake regulation in children and could also represent a risk factor for
excessive weight gain. The proposed 2-site research study uses a longitudinal cohort design in 102 children
aged 9–11 yr including baseline MRI and functional MRI (fMRI), in-depth eating behavior testing, and
measurement of hormone profiles. Serial measurement of weight and self-reported eating habits will occur
over 2 yr, with a repeated MRI at 2 yr. The study aims to: 1) test if MBH gliosis is associated with impaired
intake regulation and poor weight outcomes over 2 yr in children, 2) determine if CNS appetitive processing is
negatively affected when evidence of MBH gliosis is present, and 3) test for other brain regions in which gliosis
is present in association with excess adiposity in children. An exploratory aim will assess changes in gliosis in
children over 2 yr and their relation to changes in body weight and adiposity. In sum, basic science advances
have identified hypothalamic cellular responses that facilitate weight gain during times of nutritional
abundance. However, this neurobiological process is capable of forming glial scars that are detrimental to
neuronal functioning. The proposed study represents the first investigation of whether gliosis within body-
weight regulating areas of the hypothalamus has implications for appetite regulation and weight trajectories in
children. As such, the potential insights could trigger entirely new lines of investigation at both the basic
science and translational level. Clinically, findings could foster an expansion of our conception of children's
eating behavior from a modifiable risk factor (i.e., indicative of poor choices) to a neurobiologically-mediated
symptom requiring targeted pharmacologic, behavioral, ...

## Key facts

- **NIH application ID:** 10093020
- **Project number:** 5R01DK117623-03
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ellen A Schur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $720,978
- **Award type:** 5
- **Project period:** 2019-03-06 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10093020

## Citation

> US National Institutes of Health, RePORTER application 10093020, Impact of hypothalamic gliosis on appetite regulation and obesity risk in children (5R01DK117623-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10093020. Licensed CC0.

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