# Amylin modulates food reward

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2022 · $592,399

## Abstract

Summary
 Overweight/obesity affects more than 70% of US adults creating an enormous health and
economic burden, yet effective non-invasive treatments are limited, underscoring the importance
of identifying new pharmacotherapies that promote and sustain reductions in food intake and body
weight. Amylin receptor agonists reduce food intake and body weight in both humans and animal
models, providing a platform for the development of new amylin-based pharmacotherapies to treat
obesity. Our work identifies amylin signaling in the mesolimbic reward system as a key substrate in
the control of feeding and food reward-motivated behaviors. In a series of complementary
manuscripts, we showed that ventral tegmental area (VTA) amylin receptors are essential for the
control of palatable food intake via downstream suppression of dopaminergic signaling to the
nucleus accumbens (NAc). While these combined studies highlight the VTA as a neural substrate
for amylin's control of food reward, the behavioral and physiological mechanisms, neurochemical
phenotype(s), and additional amylin modulated circuitry within the CNS that control food reward
remain unknown. As the neural control of body weight involves the contribution of many nuclei,
clearly the most effective of future amylin-based anti-obesity pharmacotherapies will be those that
act in multiple CNS sites to modulate motivated feeding. To this end, we will investigate the
hypothesis that amylin signaling within the lateral dorsal tegmental nucleus (LDTg) and the dorsal
vagal complex (DVC) of the brainstem modulate food reward by influencing VTA neural activity.
Preliminary studies also provide compelling rationale to explore endogenous amylin signaling in
the NAc in control of behaviors directed at food reward. Using innovative approaches, we will
investigate the following aims. Aim I: Investigate the endogenous contribution and underlying
neuroanatomical circuitry of LDTg and DVC amylin receptor expressing neurons in the control of
food reward. Aim II: Examine the neural activity of VTA dopaminergic and GABAergic neurons
that are downstream of DVC or LDTg amylin receptor activation. Aim III: Investigate the
contribution of amylin receptor signaling on D1 and D2 receptor expressing neurons in the NAc
in the control of food intake and modulation of food impulsivity.

## Key facts

- **NIH application ID:** 10470394
- **Project number:** 5R01DK105155-05
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** MATTHEW R HAYES
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $592,399
- **Award type:** 5
- **Project period:** 2016-06-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470394

## Citation

> US National Institutes of Health, RePORTER application 10470394, Amylin modulates food reward (5R01DK105155-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10470394. Licensed CC0.

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