# Spinal cord injury causes liver pathology and metabolic dysfunction

> **NIH NIH R01** · OHIO STATE UNIVERSITY · 2022 · $537,485

## Abstract

Spinal cord injured (SCI) individuals have significantly reduced lifespans compared to the general population, a
statistic that has not changed in 30 years. One reason is “endocrine, metabolic and nutritional diseases”, which
are increasing at alarming rates in the SCI population (2019 Models Systems report). This is evidenced by SCI
individuals having increased prevalence of Metabolic Syndrome (MetS), the complications of which put them at
a higher risk for diabetes, cardiovascular disease and stroke compared to the general population. A central
feature of MetS and contributor to morbidity is hepatic pathology in the form of non-alcoholic steatohepatitis
(NASH), a severe form of nonalcoholic fatty liver disease (NAFLD). NASH includes hepatic lipid accumulation
(steatosis) and inflammation, which in turn cause hepatocyte damage and release of pro-inflammatory
mediators. NASH likely facilitates subsequent systems-wide pathology after SCI. Experiments in this proposal
are designed to identify mechanisms that initiate and sustain NASH in acute and chronic SCI. Focus will be on
increased sympathetic input to the liver and consequent intracellular changes in the liver that drive
inflammation and fat accumulation. We hypothesize that excess sympathetic input to the liver after SCI
initiates pro-inflammatory cascades involving TNFa and NFkB, which in turn initiate hepatic fat
accumulation and prolonged inflammation. We will use transgenic mouse technology as well as unbiased -
omics approaches to comprehensively identify cellular changes in the liver induced by SCI that drive
“neurogenic” NASH and subsequent features of MetS. Our long-term goal is to identify therapeutic targets that
can interrupt the dysfunctional spinal cord/liver axis after SCI to restore liver homeostasis and improve overall
metabolic health.

## Key facts

- **NIH application ID:** 10377530
- **Project number:** 5R01DK126008-02
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** DANA M MCTIGUE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $537,485
- **Award type:** 5
- **Project period:** 2021-04-01 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10377530

## Citation

> US National Institutes of Health, RePORTER application 10377530, Spinal cord injury causes liver pathology and metabolic dysfunction (5R01DK126008-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10377530. Licensed CC0.

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