# Extrahypothalamic PPARs and compulsive food intake

> **NIH NIH R21** · SCRIPPS RESEARCH INSTITUTE, THE · 2021 · $241,875

## Abstract

Abstract
Many people with obesity or binge eating show addiction-like behavioral changes that can be modeled in
rodents with intermittent, extended access to palatable food. New neurobiological understanding of and
therapeutic targets for compulsive eating are needed. PPARs are lipid-sensing transcription factors encoded
by 3 genes (PPARα, PPARγ, PPARβ/δ) that were identified for their roles in peripheral regulation of fuel
homeostasis. PPARα and PPARγ also have received intense attention for their anti-addiction-like actions. Yet,
the role of brain PPARδ receptors in the control of compulsive eating, which has overlapping striatal substrates
with alcohol and substance use disorders, is entirely unknown. Here, we test the overarching hypothesis that
brain peroxisome proliferator-activated receptors-delta subtype (PPARδ) inhibit addiction-like, aspects of
eating. With a novel blood-brain barrier-penetrant selective PPARδ agonist (KD3010) and cre/lox tools to
manipulate PPARδ function now available, the proposed studies address these gaps in the field and may yield
new translational approaches and insight into the biology of brain PPARδ and their role in the control of
compulsive eating and potentially other addiction phenotypes. Using an innovative, drug abuse-like mouse
model, based on intermittent, extended access to highly palatable food, Aim 1 tests the roles of central vs.
peripheral PPARδ receptors in compulsive-like food intake. Guided by preliminary data, Aim 2 test the
functional role of PPARδ receptors in dopamine Drd2/Adora2a- vs Drd1- expressing medium spiny neurons.
The resulting data and novel genetic and translationally-relevant pharmacological tools for this understudied
PPARδ isotype will lay the groundwork for cell type- and anatomically-specific mechanistic studies and may
lead to interventions for people affected by compulsive eating and potentially other forms of addiction.

## Key facts

- **NIH application ID:** 10074553
- **Project number:** 5R21DA046865-02
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **Principal Investigator:** ERIC P ZORRILLA
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $241,875
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10074553

## Citation

> US National Institutes of Health, RePORTER application 10074553, Extrahypothalamic PPARs and compulsive food intake (5R21DA046865-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10074553. Licensed CC0.

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