# Reducing adipose tissue dysfunction and metabolic complications by manipulating sensory processing after spinal cord injury

> **NIH NIH R56** · OHIO STATE UNIVERSITY · 2024 · $545,612

## Abstract

ABSTRACT
Half of the spinal cord injury (SCI) individuals experience weight gain attributed to increased adiposity.
Following SCI, increased lipid deposition is also observed in other organs including the liver, heart and skeletal
muscle. Accumulating evidence indicates that pathological expansion of adipose tissue and ectopic lipid
accumulation increases the risk of cardiometabolic disorders including hypertension, dyslipidemia and insulin
resistance. Under physiological conditions, an excess of energy is stored in adipose tissue in the form of
triglycerides. During energy deprivation, the adipose tissue mobilizes triglycerides into fatty acids via lipolysis,
and these are used as fuel for brown adipose tissue, heart, liver, and muscle. When energy balance becomes
dysregulated, ectopic accumulation of lipids in the liver and muscle as well as unresolved inflammation in
adipose tissue contribute to insulin resistance. Whether the underlying cause of metabolic complications after
SCI may be linked to adipose tissue dysfunction is unclear. Also unknown are the mechanisms that cause or
contribute to pathophysiological changes in white adipose tissue (WAT) structure and function after SCI. The
sympathetic nervous system and sensory neurons with cell bodies located in dorsal root ganglia (DRG)
innervate WAT. Whereas the contribution of sympathetic innervation to WAT function has been characterized,
the extent to which sensory innervation drives WAT function under normal and pathophysiological conditions
has remained elusive. We and others have demonstrated a remarkable convergence between neuronal
circuits' structural and functional organization and expression of α2δ subunits of voltage-gated calcium
channels (VGCC). α2δ subunits positively regulate synaptic transmission by increasing plasma membrane
expression of VGCC. However, these subunits may also play a pathological role following neuronal injury. Our
preliminary data suggest that SCI exacerbates lipolysis in epididymal (e)WAT and that α2δ1 expression
increases after a thoracic SCI in calcitonin gene-related peptide (CGRP) DRG neurons that project to eWAT.
Concurrently, we found elevated CGRP content in eWAT and increased expression of the CGRP receptor
RAMP1 in eWAT seven days after SCI. Not only does CGRP activate lipolysis independent of sympathetic
drive, but it also acts as a potent vasodilator. Changes in adipose tissue microcirculation have been associated
with health complications including adiposity and altered metabolism. Accordingly, experiments in Aim 1 will
evaluate the extent to which α2δ1 silencing and pharmacological blockade normalize eWAT function after SCI.
Aim 2 will dissect the cellular mechanism underlying α2δ1-dependent changes in eWAT lipolysis. Aim 3 will
explore the role of vascular cells in eWAT dysfunction and inflammation after SCI. Successful completion of the
proposed study may provide novel insight into molecular causes and mechanistic underpinning of maladaptive
...

## Key facts

- **NIH application ID:** 11168263
- **Project number:** 1R56NS134824-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Andrea Tedeschi
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $545,612
- **Award type:** 1
- **Project period:** 2024-09-11 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/11168263

## Citation

> US National Institutes of Health, RePORTER application 11168263, Reducing adipose tissue dysfunction and metabolic complications by manipulating sensory processing after spinal cord injury (1R56NS134824-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/11168263. Licensed CC0.

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