# Unraveling the role of PVH BDNF neurons in energy balance

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2022 · $603,054

## Abstract

Summary
The long-term goal of this research project is to understand the mechanism that regulates energy balance. In
the United States 35% of adults and 17% of youth are obese in 2011-2012. Obese youth and adults are
developing type 2 diabetes at high rates and are at significant risk for life-threatening cardiovascular
disease and cancer. Elucidation of the mechanism governing energy balance should provide an
opportunity to develop novel effective and non-invasive therapeutic interventions. Brain-derived
neurotrophic factor (BDNF) plays a critical role in regulating energy balance. Mutations in the genes for BDNF
and its receptor TrkB lead to severe obesity in both mice and humans. Furthermore, the BDNF gene has been
associated with human obesity in genome-wide association studies. However, we currently know much less
about BDNF than leptin and MC4R with regard to the mechanisms underlying the role of these molecules in
the control of energy balance. To help fill this knowledge gap, this research project tests the hypothesis that
BDNF-expressing neurons in the paraventricular hypothalamus (PVHBDNF) integrate signals related to nutrients,
energy store and reproduction, and project to both intra- and extra-hypothalamic targets to regulate appetite
and energy expenditure. This hypothesis is based on the exciting findings we made during the prior grant
period: (1) Deletion of the Bdnf gene in the PVH leads marked hyperphagia, impaired thermogenesis in brown
adipose tissue (BAT) and severe obesity; (2) PVHBDNF neurons are polysynaptically connected to BAT through
sympathetic preganglionic neurons in the spinal cord to stimulate adaptive thermogenesis; (3) PVHBDNF
neurons are also polysynaptically connected to white adipose tissue (WAT), suggesting their role in induction
of beige adipocytes; (4) PVHBDNF neurons project densely to the arcuate nucleus of the hypothalamus (ARH),
dorsomedial hypothalamus (DMH), ventral region of the lateral parabrachial nucleus (LPBN) and nucleus of the
solitary tract (NTS) in addition to the spinal cord; (5) PVHBDNF neurons receive inputs from the ARH, DMH and
rostral periventricular region of the 3rd ventricle (RP3V). As PVHMC4R neurons receive input from the ARH and
project densely to the central LPBN, NTS and dorsal motor nucleus of the vagus, our findings indicate that
PVHBDNF neurons and PVHMC4R neurons have distinct projection targets and input sources, suggesting that
these two groups of neurons regulate energy balance in different contexts. Therefore, it is imperative to
delineate neural circuits through which BDNF suppresses appetite and promotes thermogenesis in order to
fully understand the central control of energy balance. We propose to test our hypothesis in three specific
aims. Aim 1 is to identify which PVHBDNF projection regulates energy balance; Aim 2 is to determine the identity
and function of afferent neurons to PVHBDNF neurons; Aim 3 is to investigate the role of PVHBDNF neurons in
induction of bei...

## Key facts

- **NIH application ID:** 10393558
- **Project number:** 6R01DK103335-08
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** BAOJI XU
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $603,054
- **Award type:** 6
- **Project period:** 2015-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10393558

## Citation

> US National Institutes of Health, RePORTER application 10393558, Unraveling the role of PVH BDNF neurons in energy balance (6R01DK103335-08). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10393558. Licensed CC0.

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