# Regulation of energy and glucose balance through BDNF signaling in VMH astrocytes

> **NIH NIH F31** · TUFTS UNIVERSITY BOSTON · 2020 · $24,392

## Abstract

PROJECT SUMMARY/ ABSTRACT
 Energy and glucose homeostasis are complex processes controlled in part by central neural circuits.
Within the brain, the hypothalamus receives and integrates peripheral energy status signals and responds by
altering feeding behavior and energy expenditure to meet the nutritional demands of the organism. Brain-
derived neurotrophic factor (BDNF) signaling in the ventromedial hypothalamus (VMH) is critical for the
regulation of food intake, body weight and glucose balance. Expression of BDNF is robustly induced in the fed
state, where BDNF activation of its neuronal receptor tyrosine receptor kinase B (TrkB) drives activity of
anorexigenic VMH neurons to decrease food intake and lower blood glucose levels. BDNF mutations in both
mouse models and in humans are associated with severe obesity and impaired glycemic control. In addition to
its robust effects on neuronal plasticity, BDNF has been shown to regulate astrocyte morphology and calcium
signaling through activation of a TrkB splice variant, TrkB.T1. It is well established that astrocytes play an
active role regulating neuronal activity. They are in contact with the blood supply and communicate with
neurons, which make them an excellent yet understudied candidate for sensing peripheral metabolic signals to
accordingly shape the appropriate neuronal and metabolic responses. The proposed work will test the
hypothesis that VMH astrocytes are key regulators of energy and glucose balance, and that BDNF
signaling in this cell population is critical for these effects. In support, preliminary data suggest that BDNF
and energy status dynamically regulate function and structural plasticity of VMH astrocytes to mediate energy
balance control. Proposed experiments will use advanced behavioral, molecular and electrophysiological
techniques to ascertain the role of VMH astrocyte BDNF/TrkB.T1 signaling on energy and glucose balance,
and examine the effects of BDNF/TrkB.T1 signaling on VMH astrocyte-neuron interactions.
 A better understanding of the central circuitry and cell types controlling energy and glucose balance is
required for treatment of our nations obesity epidemic. The proposed study will inform novel molecular
mechanisms involved in the regulation of central feeding circuits and provide a stepping-stone for identification
of potential therapeutic targets in treating obesity and metabolic disorder. Importantly, the novel hypothesis and
multifaceted experiments proposed will provide an excellent training opportunity for me as a developing
scientist in the field of central control of energy and glucose balance.
!

## Key facts

- **NIH application ID:** 10000136
- **Project number:** 5F31DK118789-03
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Dominique Ameroso
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $24,392
- **Award type:** 5
- **Project period:** 2018-09-16 → 2021-02-15

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10000136

## Citation

> US National Institutes of Health, RePORTER application 10000136, Regulation of energy and glucose balance through BDNF signaling in VMH astrocytes (5F31DK118789-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10000136. Licensed CC0.

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