# Interactions of Leptin and the Melanocortin System

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2024 · $435,267

## Abstract

PROJECT SUMMARY
The increasing rates of obesity and diabetes highlight the need to understand the brain circuits and cellular
mechanisms regulating energy balance and glucose homeostasis. Prominent among these is the central leptin-
melanocortin system, which includes the pro-opiomelanocortin (POMC) neurons, subsets of which express
leptin receptors (LEPRs). While enormous strides have been made to understand the role of hypothalamic
POMC neurons that produce α-MSH in metabolism, relatively little is known about how the three isoforms of -
MSH produced in hypothalamus and pituitary gland POMC-expressing cells respond to metabolic challenges.
The current application extends our previous discovery that LEPR-expressing POMC neurons are required for
coordinating hepatic glucose production and responding to metabolic challenges. We will determine the roles
for -MSH peptides produced from POMC neurons in the regulation of metabolism in dynamic challenges. This
project is also significant because it will be the first to combine the power of mouse genetics with advanced
mass spectrometry to quantitatively measure and map specific POMC-derived -MSH peptides in
hypothalamic and pituitary tissues. We will also correlate -MSH peptide levels with parameters of energy and
glucose homeostasis, and deermine which peptides underlie metabolic adaptation. These studies will broaden
our understanding of the functional mechanism by which the leptin-melanocortin system regulates endocrine
and autonomic functions, particularly at the level of liver and adipose tissues.

## Key facts

- **NIH application ID:** 10894756
- **Project number:** 5R01DK118725-06
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** JOEL K. ELMQUIST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $435,267
- **Award type:** 5
- **Project period:** 2018-09-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10894756

## Citation

> US National Institutes of Health, RePORTER application 10894756, Interactions of Leptin and the Melanocortin System (5R01DK118725-06). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10894756. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*