# PACAP - leptin interaction in the hypothalamic ventromedial nuclei in the regulation of energy homeostasis

> **NIH NIH R15** · MARQUETTE UNIVERSITY · 2020 · $13,006

## Abstract

Project Summary/Abstract
 The impact of the obesity epidemic in the US has been estimated to endanger the health of up to
30% of Americans by increasing the risk of diabetes, hypertension, stroke, and cancer as well as
leading to 300,000 deaths annually. In order to lessen the negative impact of obesity, there is a need
to better understand the neurobiology of feeding and metabolism in a manner that could contribute to
the development of effective therapeutics. Attempts to understand the neural basis of feeding and
metabolism often involve the study of individual neuropeptides that alter caloric intake and/or energy
expenditure. Anatomical studies have implicated subregions of the hypothalamus as sites of action
for several dozen peptide regulators of feeding behavior and body weight. Specifically, the
ventromedial nuclei of the hypothalamus (VMN) exert powerful control over feeding and metabolism
through a broad array of both central and peripheral signaling molecules. For example, leptin, a well-
studied peripheral signal produces hypophagia when administered into the VMN. Centrally, the
actions of the VMN on energy homeostasis are also dependent on the activity of neural inputs
synthesized and released by other brain regions such as the neuropeptide, pituitary adenylate
cyclase activating polypeptide (PACAP), which promotes energy expenditure and decreases feeding
behavior. Thus, neurons in the VMN likely integrate both neural and peripheral signals in order to
regulate energy homeostasis.
 Preliminary data in this proposal support the hypothesis that leptin and PACAP interact in the VMN
by regulating shared intracellular signaling pathways that lead to hypophagia. This is not surprising
given the common and parallel features between PACAP and leptin in terms of anatomy, behavioral
and metabolic outcomes, gene activation patterns, and functional dependency. This proposal
examines several points of convergence among the intracellular signals produced by leptin and
PACAP including the JAK-STAT signaling cascade and BDNF expression. Moreover, PACAP and
leptin are ideal candidates to study the functional interactions between a tonically peripheral signal
and a synaptically released neuropeptide that together could alter the activity of a broad neural
network responsible for feeding behavior and energy homeostasis. In the hypothalamic VMN, we will
examine the intracellular signaling links between PACAP and leptin (aim 1), and the functional
relationship between PACAP and leptin under chronic conditions of leptin receptor dysregulation with
obesity, hyperleptinemia without obesity, and diet induced obesity (aim 2).

## Key facts

- **NIH application ID:** 10063218
- **Project number:** 3R15DK113608-01A1S1
- **Recipient organization:** MARQUETTE UNIVERSITY
- **Principal Investigator:** SuJean Choi
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $13,006
- **Award type:** 3
- **Project period:** 2017-09-01 → 2020-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10063218

## Citation

> US National Institutes of Health, RePORTER application 10063218, PACAP - leptin interaction in the hypothalamic ventromedial nuclei in the regulation of energy homeostasis (3R15DK113608-01A1S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10063218. Licensed CC0.

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