# Molecular and Neural Mechanisms of Leptin Action

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $464,877

## Abstract

Abstract
 Obesity represents a burgeoning health threat that predispose millions of people to reduced life
expectancy; additionally, obese people incur $2741 higher annual healthcare costs than normal-weight
individuals. Unfortunately, few effective medical options exist for the prevention or treatment of obesity. To
design effective treatments, we must understand the mechanisms that mediate energy homeostasis. Leptin and
its receptor (LepRb) play crucial roles in the control of energy balance. Understanding the molecular and neural
mechanisms of leptin action represents the long-term goal of our previous and proposed studies under this
project (DK056731).
 Our findings to date have revealed the importance of STAT3 and a second, pY-independent, LepRb
signal for leptin action; have determined the transcriptional targets (potential downstream mediators) of leptin;
and have identified crucial neuronal mediators of leptin action. We propose to understand the molecular and
neural mechanisms of leptin action by: 1: Testing the hypothesis that specific genes regulated by leptin in LepRb
neurons play crucial roles in leptin action and the control of energy balance. 2: Testing the hypothesis that the
deletion of specific pY-independent regions of LepRb will alter the leptin-mediated control of neuronal function
and energy balance, despite intact STAT3 signaling. 3: Testing the hypothesis that distinct subpopulations of
hypothalamic LepRb neurons control POMC and AgRP neurons to modulate energy homeostasis.
 Overall, these studies will define the molecular and neural mechanisms by which leptin controls energy
balance. These pathways may be dysregulated in disease and may represent targets for therapeutic
intervention.

## Key facts

- **NIH application ID:** 10201574
- **Project number:** 5R01DK056731-23
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Martin G Myers
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $464,877
- **Award type:** 5
- **Project period:** 1999-03-15 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10201574

## Citation

> US National Institutes of Health, RePORTER application 10201574, Molecular and Neural Mechanisms of Leptin Action (5R01DK056731-23). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10201574. Licensed CC0.

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