# GLP-1 analogue effects on food cues, stress, motivation for highly palatable foods, and weight

> **NIH NIH R01** · YALE UNIVERSITY · 2020 · $700,823

## Abstract

ABSTRACT
The United States is at the forefront of the global obesity epidemic. To understand the mechanisms driving
increases in obesity, this first cycle of the R01-DK099039 project developed and validated a novel laboratory
model for overeating highly palatable (HP) foods in the context of HP food cue and stressful environments, both
of which are associated with weight gain and obesity risk. Findings supported that BMI-related adaptations in
cortisol, ghrelin, insulin sensitivity, HP food craving and hunger each predicted HP overeating in a Food Snack
Test (FST) in a laboratory experiment, and remarkably, these measures also prospectively predicted weight gain
over a longitudinal 2-year outcome period. Recent data suggests glucagon-like peptide-1 (GLP-1) modulates
stress biology along with its effects on metabolism. Preliminary work by led by Dr. Jastreboff indicate GLP-1
analogue (GLP-1a) treatment decreases craving, hunger and food intake in both the laboratory and real-world
setting. Thus, in this competitive renewal, we propose a multi-PI experimental therapeutics approach with the
GLP-1a, semaglutide, in the unique and predictive laboratory model developed in the current project to test the
hypothesis that GLP-1a treatment will attenuate HP food cue- and stress-induced food motivation and intake in
obesity and also improve metabolic and stress responses and such changes will predict weight outcomes. A
randomized, double-blind, placebo-controlled 12-week study with GLP-1a in men and women (N=96) with
obesity (BMI 30-39.9 kg/m2) is proposed to test the above overall hypothesis both in a laboratory experiment
and over a 12 -week treatment period to assess real-world outcomes. Specific aims are: 1) to examine the effects
of GLP-1a vs. PBO treatment on food craving, hunger, food-cue- and stress- induced FST intake and eating
topography in the FST; 2) to assess the effects of GLP-1a vs. PBO treatment on weekly food craving and food
calorie intake in the real-world setting during the 12-week treatment period; and 3) to examine the effects of
GLP-1a treatment on metabolic and stress responses (ghrelin, cortisol, and insulin resistance) on HP food
craving and intake in the experimental lab model of food craving and FST intake. Exploratory aims will GLP-1a
changes in laboratory outcomes predict weight outcomes and whether specific factors such as gender, chronic
stress, disordered eating, diet and physical activity affect outcomes. Utilizing a novel experimental therapeutics
approach, the next phase of this project will apply the current cycle’s validated laboratory model of identifying
processes underlying greater HP food craving, intake and weight gain to test mechanisms by which a GLP-1a
analogue exerts significant weight effects in obesity. Positive findings will not only inform how GLP-1a exerts
effects on weight, but also provide a unique, stress and food cue sensitive, innovative and cost-effective human
laboratory approach for testing novel ...

## Key facts

- **NIH application ID:** 10051202
- **Project number:** 2R01DK099039-06
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Ania Jastreboff
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $700,823
- **Award type:** 2
- **Project period:** 2013-07-15 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051202

## Citation

> US National Institutes of Health, RePORTER application 10051202, GLP-1 analogue effects on food cues, stress, motivation for highly palatable foods, and weight (2R01DK099039-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10051202. Licensed CC0.

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