# Hindbrain astrocytes mediate the energy balance effects of Leptin

> **NIH NIH F32** · UNIVERSITY OF PENNSYLVANIA · 2020 · $72,006

## Abstract

PROJECT SUMMARY
The staggering prevalence of obesity in the United States poses major public health concerns. Since
energy balance regulation is coordinated by CNS centers, investigation into the underlying
homeostatic, brain mechanisms controlling feeding behavior and weight management is critical to the
development of novel and efficacious obesity therapeutics. The proposed research focuses on the
role of astrocytes in the nucleus tractus solitarius (NTS) of the caudal brainstem in mediating the food
intake and body weight suppressive effects of adipocyte derived hormone leptin. While the vast
majority of studies have investigated neuronal processing of leptin signaling, little is known about the
contribution of non-neuronal cells such as astrocytes. Collectively, the critical role of astrocytes in
modulating neuronal excitability, synaptic efficiency, and plasticity of metabolic circuits in addition to
recent evidence demonstrating expression of the leptin receptor (LepRb) on astrocytes, suggests
NTS astrocytes are a prime cellular target for central leptin signaling. The main goal of this
proposal is to train the fellowship applicant in a variety of in vivo techniques to investigate the
role of caudal brainstem LepRb-expressing astrocytes in the integration of energy status
signals and the long-term reductions in food intake and body weight produced by LepRb
activation in both male and female rats. Preliminary evidence shows that pharmacological
blockade of NTS astrocytes significantly attenuates the acute hypophagic effect of centrally
administered leptin. Therefore, Specific Aim I tests the hypothesis that NTS astrocytes are
pharmacologically and physiologically relevant in mediating the energy balancing effects of leptin.
Leptin's influence on energy balance also occurs, in part, by potentiating neuronal processing of
gastrointestinal (GI)-derived satiation signals at the level of the caudal brainstem. Specific Aim II
involves a series of behavioral and neuroanatomical experiments to examine this potential
contribution of NTS astrocytes in modulating GI-derived satiation signals and the synergistic
interaction between NTS leptin signaling and these GI satiation signals. An important component of
these proposed aims is to (1) investigate the effects of high fat diet on astrocytic leptin signaling and
(2) identify any potential sexual dimorphisms in the contribution of NTS astrocytes to control energy
balance. Overall, results from these experiments will determine the functional relevance of LepRb
signaling on NTS astrocytes in metabolic homeostasis and/or as novel target for the treatment of
obesity and importantly prepare the fellow for an independent research career.

## Key facts

- **NIH application ID:** 10007825
- **Project number:** 5F32DK118818-03
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Lauren Michelle Stein
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $72,006
- **Award type:** 5
- **Project period:** 2018-09-05 → 2022-03-03

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10007825

## Citation

> US National Institutes of Health, RePORTER application 10007825, Hindbrain astrocytes mediate the energy balance effects of Leptin (5F32DK118818-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10007825. Licensed CC0.

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