# Control of feeding behavior by melanin-concentrating hormone

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2024 · $543,312

## Abstract

Project Summary
 Given that eating frequency is largely determined by societal norms, a deeper understanding of the
neural substrates that control meal size is critical for the development of novel and more effective treatments
for obesity. The amount of food consumed over the course of a meal is determined by a competing balance
between an early-meal positive feedback process called appetition and a late-meal negative feedback process
called satiation. We hypothesize that melanin-concentrating hormone (MCH), an orexigenic neuropeptide
produced in the lateral hypothalamic area (LHA) and zona incerta (ZI), is critical in mediating the poorly
understood process of appetition. While such a role for MCH has not been directly investigated, this notion is
supported by findings revealing that MCH neurons are glucose responsive 1,2 and MCH injections augment food
intake by increasing meal size 3. A role for MCH signaling in mediating appetition is further supported by our
preliminary data showing that chemogenetic activation of MCH neurons (LHA + ZI populations) potentiates
flavor preference learning for a nonnutritive flavor paired with intragastric glucose infusion.
 MCH is produced in both the LHA and the ZI, which are adjacent regions that are differentiated both
functionally and neuroanatomically 4-7. Our preliminary results, using fiber photometry to measure MCH
neuron calcium activity in awake behaving animals, reveal that LHA and ZI MCH neurons show distinct
calcium activity dynamics during a meal, such that LHA MCH neuron activity increases during active eating
relative to interbout intervals, and ZI MCH neuron activity shows the opposite pattern (activity elevated during
interbout intervals relative to active eating). These findings introduce the possibility that LHA and ZI MCH
neurons subserve distinct but complementary functions in the control of feeding. Based on our preliminary
data, here we will evaluate our hypothesis that LHA MCH neurons promote orosensory-mediated appetition,
and ZI MCH neurons promote post-oral nutritive-mediated appetition. This hypothesis will be evaluated by
separately targeting LHA vs. ZI MCH neuron populations in Aim 1 experiments measuring physiological MCH
neuron calcium activity in response to orosensory vs. post-oral nutrient sensing in lean and obese rats, and in
Aim 2 functional chemogenetic and caspace-mediated ablation experiments determining the precise oral and
post-oral mechanisms through which MCH neuron activation promotes flavor-nutrient learning.
 In addition to exploring the physiological responses (Aim 1) and functional relevance (Aim 2) of the two
MCH neuron populations with regards to appetition and food intake, Aim 3 will combine MCH neuron
population-specific pathway tracing, metabolic brain mapping, and single-nucleus RNA sequencing
approaches to extensively characterize the anatomical, network, and transcriptional profiles of ZI vs. LHA
MCH neurons. Overall, these complementary aims will sig...

## Key facts

- **NIH application ID:** 10890536
- **Project number:** 2R01DK118402-05A1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Scott Edward Kanoski
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $543,312
- **Award type:** 2
- **Project period:** 2018-07-23 → 2029-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890536

## Citation

> US National Institutes of Health, RePORTER application 10890536, Control of feeding behavior by melanin-concentrating hormone (2R01DK118402-05A1). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10890536. Licensed CC0.

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