# Deconstructing the Neural Control of Food Seeking

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $402,500

## Abstract

Summary.
The dramatic increase in obesity and associated comorbidities in the United States is a major public health
concern. While weight loss improves these conditions, widespread difficulty in implementing successful diets
and high recidivism are major barriers to effective obesity treatments. The objective of this proposal is to
identify neuron subpopulations and define neural mechanisms that impede weight loss. Agouti-related protein
(AgRP)-expressing neurons in the arcuate nucleus of the hypothalamus are activated by energy deficit and
motivate food seeking and consumption. We have demonstrated that AgRP neurons transmit a negative
valence signal that may underlie the negative affect often associated with hunger and weight loss. Thus, there
is a critical need to identify how AgRP neurons communicate with other brain regions to drive negative
valence, food seeking, and consumption. AgRP neurons can be divided into distinct subpopulations that
project to one of several target brain regions, but our understanding of the distinct AgRP projection
subpopulations that mediate the physiological and affective consequences of AgRP neural activity remains
incomplete. To this end, the complementary aims in this proposal use state-of-the-art techniques to
characterize, with unprecedented levels of detail, the AgRP neuron projection subpopulations and circuit
mechanisms that drive food intake. Specifically, our experiments will (1) identify the distinct AgRP projection
subpopulation(s) that mediate the negative valence associated with hunger, (2) determine the endogenous
activity patterns of AgRP subpopulations during the transition between replete and deprived physiological
states, (3) examine how AgRP subpopulation activity changes with obesity, and (4) determine the AgRP
projection subpopulations that contribute to the motivation to work for food. Overall, results from these
experiments will identify brain regions that are physiologically and functionally recruited by AgRP neuron
activity, providing novel neural substrate targets that can be leveraged to develop potent therapies for obesity.

## Key facts

- **NIH application ID:** 9923452
- **Project number:** 5R01DK114104-04
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** John Nicholas Betley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $402,500
- **Award type:** 5
- **Project period:** 2017-07-17 → 2022-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9923452

## Citation

> US National Institutes of Health, RePORTER application 9923452, Deconstructing the Neural Control of Food Seeking (5R01DK114104-04). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9923452. Licensed CC0.

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