# The Role of the PBN Melanocortin System in the Regulation of Ingestive Behaviors

> **NIH NIH K99** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $91,380

## Abstract

PROJECT SUMMARY
Internal and external sensory processes monitor metabolic signals and subsequently promote or suppress
appetite. The parabrachial nucleus complex (PBN), composed of numerous subnuclei, is a fundamental sensory
hub important for taste processing, appetite regulation, and initiating appropriate feeding responses. While
several neuronal markers have been identified to play an important role in feeding and adaptive behaviors within
the PBN, markers that integrate the complex inputs that the PBN receives are unknown – particularly those that
can increase feeding. Furthermore, it is well-established that melanocortin receptors (MC3R and MC4R) and
their ligands, AgRP and POMC, play essential roles in regulating feeding behavior. Moreover, it has been well-
established that the melanocortin receptors (MC3R and MC4R) and their ligands, AgRP and POMC, are essential
components in regulating feeding behavior. We have identified that MC4R-expressing cells and MC4R in the
PBN lead to several profound suppressions of food and fluid, impaired fast-refeeding hyperphagia, the presence
of anxiety-induced feeding, and orosensory incoordination. These complex phenotypes illustrate the crucial role
of MC4R activation in generalized ingestive behaviors, yet the mechanisms underlying these behaviors remain
unknown. In contrast, pharmacological activation of the MC3R in the PBN directs mice to consume more food.
We know that the global deletion of the MC4R has an opposing phenotype of those observed in the global
knockout of the MC3R, illustrating that a relationship between MC3R and MC4R in the PBN to integrate opposing
ingestive behaviors is highly plausible. As a first step in testing this hypothesis, the following three aims will be
examined: 1) Defining the neuroanatomical organization of the MC4R and MC3R in the PBN, 2) Characterizing
the activity of the PBN-MC4R in appetite suppression, and finally, 3) Characterizing the activity of PBN-MC3R
neurons in consummatory behavior. To accomplish the goals of this project, Dr. Dahir will receive unparalleled
and complementary training in neuroanatomy, functional circuit analyses, and pharmacology from her mentoring
committee, Dr. Cone, Dr. Simerly, and Dr. Palmiter. The outcomes of this project will shed light on
melanocortinergic signaling within the PBN in response to ingestive behavior, ultimately contributing to the
advancement of therapeutic strategies. Furthermore, training under this K00/R00 application will provide Dr.
Dahir with the necessary technical and conceptual background to start her independent research program
focusing on the effects of sensory processes in ingestive behaviors.

## Key facts

- **NIH application ID:** 10947852
- **Project number:** 1K99DK140527-01
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Naima Dahir
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $91,380
- **Award type:** 1
- **Project period:** 2024-08-06 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10947852

## Citation

> US National Institutes of Health, RePORTER application 10947852, The Role of the PBN Melanocortin System in the Regulation of Ingestive Behaviors (1K99DK140527-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10947852. Licensed CC0.

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