# Central melanin-concentrating hormone neural pathways and obesity

> **NIH NIH R03** · UNIVERSITY OF GEORGIA · 2021 · $106,500

## Abstract

Project Summary/Abstract
 Despite considerable efforts to address and reverse the obesity epidemic, obesity remains highly
prevalent in the U.S. The brain plays an important role in regulating body weight, both through modulating
energy expenditure and driving feeding behavior, and thus understanding how the brain regulates energy
balance is critical for developing effective obesity treatments. Melanin-concentrating hormone (MCH) is a
neuropeptide that acts in the brain to promote weight gain by increasing food intake and reducing energy
expenditure. Due to its dual actions on both aspects of the energy balance equation, the MCH system is a
promising target for obesity pharmacotherapies. Currently, the mechanisms and neural sites of action by which
MCH modulates energy balance are largely unknown. The overarching goal of this proposal is to identify
neural sites of action and mechanisms by which MCH promotes hyperphagia and susceptibility to diet
induced obesity. Specific Aim 1A and 1B utilizes two novel virogenetic RNA interference approaches to promote
a loss of function to the MCH system in the paraventricular hypothalamus (PVH). Animals are then challenged
with a palatable high fat, high sugar, Western cafeteria diet in order to determine whether the PVH MCH
system plays a role in the development of diet induced obesity. Experiments are performed in male and female
rats, with the potential for further investigation into sex differences should sexually dimorphic effects be
observed. Specific Aim 1C investigates a novel molecular mechanism by which MCH may alter feeding effects,
namely by modulating the length of neuronal primary cilia and/or gene expression of the ciliary signaling
protein adenylyl cyclase 3 (AC3). Specific Aim 2A investigates the function of zona incerta (ZI) MCH neurons, a
population whose behavioral function has not been studied in isolation with regards to feeding behavior. Based
on our unpublished preliminary data and recent published work, we propose that ZI MCH neurons increase
binge-eating behavior. We will examine this question using our MCH neuron-specific chemogenetic DREADDs
approach. We further plan to determine the downstream anatomical outputs of ZI MCH neurons, which will
enable us to employ our dual virus chemogenetic approach in future studies in order to better understand the
function of the multi-order circuitry of this unique population of MCH neurons. These experiments build on
the experiments from the applicant's K01 proposal and are specifically designed to produce necessary data
for the applicants R01 application. The studies outlined herein will additionally contribute significantly to
understanding the role of the MCH signaling in regulating energy balance, which is an important step toward
effectively developing obesity pharmacotherapies based on this system.

## Key facts

- **NIH application ID:** 10190403
- **Project number:** 1R03DK128306-01
- **Recipient organization:** UNIVERSITY OF GEORGIA
- **Principal Investigator:** Emily Elizabeth Noble
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $106,500
- **Award type:** 1
- **Project period:** 2021-04-01 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10190403

## Citation

> US National Institutes of Health, RePORTER application 10190403, Central melanin-concentrating hormone neural pathways and obesity (1R03DK128306-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10190403. Licensed CC0.

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