# A twin study of obesity pathogenesis using fMRI

> **NIH NIH R01** · UNIVERSITY OF WASHINGTON · 2020 · $731,614

## Abstract

ABSTRACT
 The long-term health benefits of obesity treatment are limited by the weight regain that almost universally
follows a weight loss intervention, frustrating patients and clinicians alike. In lay terms, a new, higher “set point”
seems to occur after people gain weight, and research shows that processes of energy homeostasis, directed
by neurons in the arcuate nucleus of the hypothalamus, vigorously defend the higher level of adiposity for
years, promoting weight regain after behavioral weight loss. Bariatric surgery, however, results in weight loss
that is more durable over time. These phenomena remain incompletely understood. The current proposal
endeavors to address this crucial scientific gap by investigating the brain's role in the persistence of obesity
and weight regain after weight loss. Specifically, studies in rodents show that diet-induced weight gain requires
an inflammatory and cellular response, known as gliosis, within the arcuate nucleus of the hypothalamus and
that this gliosis persists with continued dietary exposure. Importantly, gliosis is detectable in mice and humans
by magnetic resonance imaging (MRI). Using MRI, the investigators discovered the first evidence of
hypothalamic gliosis in obese humans. The investigators have also shown that hypothalamic gliosis is
improved by Roux-en-Y gastric bypass (RYGB) surgery, suggesting that the efficacy and durability of weight
loss via bariatric surgery could be partially explained by its ability to reverse gliosis. New findings show that
hypothalamic gliosis negatively impacts brain regulation of appetite. Based on such findings, the proposed
research investigates novel questions about the possible implications of hypothalamic gliosis for clinical weight
management. First, it will determine whether the extent of hypothalamic gliosis present when people with
obesity start a behavioral weight loss program is related to their success in treatment or weight regain after
treatment. Second, the current proposal also addresses the question of whether gliosis is reduced to a greater
extent when weight loss occurs by RYGB than by lifestyle change alone. Finally, this investigation uses a
rodent study to test the role of 2 different hypothalamic glial cell types in weight regain after weight loss. In
sum, basic science advances have identified hypothalamic cellular responses that facilitate weight gain during
times of nutritional abundance, but this biological process is also capable of forming glial scars that are
detrimental to neuronal functioning. The current research therefore investigates the implications of
hypothalamic gliosis for humans undergoing obesity treatment. Achieving a better understanding of the role of
the brain in successful obesity treatment could open new avenues for research, intervention, and prevention to
alleviate the health risks of obesity.

## Key facts

- **NIH application ID:** 9972905
- **Project number:** 5R01DK089036-08
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Ellen A Schur
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $731,614
- **Award type:** 5
- **Project period:** 2011-09-20 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9972905

## Citation

> US National Institutes of Health, RePORTER application 9972905, A twin study of obesity pathogenesis using fMRI (5R01DK089036-08). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9972905. Licensed CC0.

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