# Interrogating Ventral Pallidal Circuits as a Therapeutic Target for Obesity

> **NIH NIH F31** · WASHINGTON UNIVERSITY · 2024 · $35,482

## Abstract

PROJECT SUMMARY
Over two-thirds of Americans are overweight or obese, with the recent rise in obesity prevalence strongly
correlated with widespread access to palatable, energy-dense foods. These foods, typically highly processed
and rich in calories, salt, sugar, and fat, exhibit extraordinary appetitive properties, leading to pathological
overeating. For instance, palatable foods can override the body's satiety signals, while regular consumption can
cause taste desensitization, making healthier options taste bland in comparison. Furthermore, it is hypothesized
that the reinforcing properties of such foods activate reward circuitry, leading to a dissociation between caloric
need (the number of calories required to maintain stable weight) and food intake (the number of calories
consumed), which ultimately results in obesity. While numerous brain areas are involved in appetite control, this
research focuses on the ventral pallidum (VP), a major relay structure in the reward system which plays a key
role in processing the pleasure and motivation associated with ingestive behavior. However, the potential to
manipulate VP activity to suppress or reverse excessive body weight remains unexplored. In this proposal, I plan
to use a multifaceted approach to investigate VP neuronal responses during palatable food consumption and
how this activity contributes to pathological consumption behavior. Since foods high in dietary fat
disproportionately affect satiety and induce hyperphagia in humans and other animals, I hypothesize that VP
neurons are more strongly activated by fat consumption than carbohydrate consumption. To test this, I will record
population calcium signals from VP neurons in head-fixed mice consuming mixtures with varying proportions of
fats and carbohydrates. With the long-term goal of evaluating whether ventral pallidal manipulations can serve
as a viable therapeutic strategy for obesity treatment, I will employ a chronic inactivation strategy on VP neurons
and assess its effectiveness in producing weight loss in obese animals. Understanding the neural basis of obesity
pathology, and specifically why fat-enriched foods induce hyperphagia, will inform the development of future
therapeutics aimed at achieving substantial weight loss in individuals with obesity.

## Key facts

- **NIH application ID:** 10995636
- **Project number:** 1F31DK138755-01A1
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** JUSTIN G WANG
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $35,482
- **Award type:** 1
- **Project period:** 2024-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10995636

## Citation

> US National Institutes of Health, RePORTER application 10995636, Interrogating Ventral Pallidal Circuits as a Therapeutic Target for Obesity (1F31DK138755-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10995636. Licensed CC0.

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