# Regulation of energy expenditure through BDNF neurons in the paraventricular hypothalamus

> **NIH NIH F32** · SCRIPPS FLORIDA · 2020 · $67,446

## Abstract

PROJECT SUMMARY/ABSTRACT
Obesity results from a chronic positive balance of energy intake and energy expenditure. To find therapeutic
targets for obesity, this proposal focuses on elucidating neural circuits that govern energy expenditure. In the
body, energy is stored as white adipose tissue (WAT) and expended in brown adipose tissue (BAT). Under
certain physiological conditions such as cold, energy is dissipated from BAT in the form of heat. Under these
same conditions, certain regions of WAT can convert to brown adipocyte-like cells, express thermogenic genes
similar to BAT, and expend energy. Brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin
receptor kinase B (TrkB), are implicit in the development of obesity. Mutations in BDNF and TrkB are
associated with obesity in humans and mice. Recently, we reported that BDNF expression in the medial/lateral
portion of the paraventricular hypothalamus (PVH) polysynaptically connects to interscapular brown adipose
tissue (iBAT). Preliminary evidence suggests that BDNF-TrkB signaling via activation of PVHBDNF neurons can
drive thermogenesis in iBAT because BDNF expression in the PVH increases in response to cold exposure. In
contrast Bdnf gene ablation causes atrophy of sympathetic preganglionic neurons en route to iBAT and
impaired thermogenesis in iBAT. Evidence also suggests that BDNF expression in the PVH stimulates
thermogenesis in WAT. We performed retrograde transneuronal tracing via injection of pseudorabies virus
(PRV) into the inguinal region of WAT (iWAT) and found infection in PVHBDNF neurons. This suggests a
polysynaptic connection between PVHBDNF neurons and iWAT. However, the functional relationship between
BDNF-TrkB signaling from PVH neurons to BAT and WAT is unknown. In the long-term I wish to explore neural
circuits that regulate energy expenditure. I hypothesize that BDNF-TrkB signaling promotes adaptive
thermogenesis in WAT and BAT. I will test this hypothesis with three aims: 1) to confirm that activation of
PVHBDNF neurons stimulates adaptive thermogenesis in BAT without affecting sympathetic inputs to the heart
and blood vessels, 2) to elucidate the synaptic properties of BDNF-TrkB signaling between PVHBDNF neurons
and cholinergic sympathetic preganglionic neurons in the spinal cord, and 3) to determine if BDNF expression
in the PVH is required to induce browning of WAT in response to cold exposure. To carry out these
experiments, I will perform viral injections on transgenic mice to control BDNF-TrkB signaling. I will also use
electrophysiology and metabolic measurements of BAT and WAT. Findings from this study will uncover an
important relationship between BDNF-TrkB signaling and energy expenditure.
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## Key facts

- **NIH application ID:** 9930585
- **Project number:** 5F32DK115099-03
- **Recipient organization:** SCRIPPS FLORIDA
- **Principal Investigator:** Shaw-wen Wu
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $67,446
- **Award type:** 5
- **Project period:** 2018-06-01 → 2021-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9930585

## Citation

> US National Institutes of Health, RePORTER application 9930585, Regulation of energy expenditure through BDNF neurons in the paraventricular hypothalamus (5F32DK115099-03). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9930585. Licensed CC0.

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