# Interactions of Leptin and the Melanocortin System

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $418,051

## Abstract

Abstract
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). Understanding how leptin differentially regulates energy balance versus glucose
homeostasis is key for the development of anti-obesity and anti-diabetes therapies. Early observations based
on prenatal genetic manipulations led to the widely-held model that LEPR-expressing POMC neurons
mediated the metabolic actions of leptin, however, evidence now suggests that these pathways are more
complex than originally anticipated. The current application extends our early developmental models by directly
testing the role of leptin action in adult melanocortin neurons in regulating glucose metabolism and responding
to dynamic challenges, including fasting and cold exposure. We also have in hand a model in which liver
insulin resistance can be induced in a temporal manner, allowing us to investigate the role of the leptin-
melanocortin pathway in its development. These studies will broaden our understanding of the functional
mechanism by which the leptin-melanocortin system regulates endocrine, autonomic, and behavioral functions,
particularly at the level of adipose tissues and liver.

## Key facts

- **NIH application ID:** 9984351
- **Project number:** 5R01DK118725-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** JOEL K. ELMQUIST
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $418,051
- **Award type:** 5
- **Project period:** 2018-09-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9984351

## Citation

> US National Institutes of Health, RePORTER application 9984351, Interactions of Leptin and the Melanocortin System (5R01DK118725-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9984351. Licensed CC0.

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