# Imaging Hepatic Energy Metabolism in NAFLD/NASH

> **NIH NIH R01** · UNIVERSITY OF FLORIDA · 2023 · $518,154

## Abstract

Project Summary
 There is an urgent need for development of metabolic imaging methods that are sensitive to nonalcoholic
fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), and to the transition linking the two
pathophysiological states. We will develop magnetic resonance based metabolic imaging using hyperpolarized
13C and thermally polarized 2H-labeled substrates. Our testbed is the C57Bl/6N mouse, and diet induced and
genetic models of the disease states. The approach assays both carbohydrate and fatty acid metabolism,
which are known to be altered in these diseases. Aim 1. Using hyperpolarized [1-13C] and [2-13C]pyruvate and
[2-13C]dihydroxyacetone, we will produce a multi-parametric assessment of hepatic pyruvate oxidation and
anaplerosis, as well as pyruvate cycling. Aim 2. Using uniformly deuterated fatty acids, we will determine rates
of β-oxidation and changes in redox biology in the same models. The combination of these approaches will
yield the most comprehensive analysis of energy metabolism to date in these well-accepted models of the
human disease. Aim 3. We will confirm both carbohydrate and fatty acid metabolism imaging assays using
knock out mice that test the assumptions underlying our paradigms. The pyruvate carboxylase knockout
mouse downregulates pyruvate anaplerosis. The fumarate hydratase knockout mouse is a model of
downregulated metabolism that will test our sensitivity to changes in Krebs cycle turnover. The acetyl-CoA
carboxylase knockout mouse will upregulate fatty acid oxidation. All three pathways have been hypothesized
as essential elements of the pathogenesis and progression of NAFLD and NASH.
Relevance
 NAFLD and NASH are now a worldwide epidemic, with some estimates of NAFLD prevalence as high as
24% of the world population. NASH is expected to surpass hepatitis as the number one cause of liver
transplant in the United States within the next 5 years. Over the next 10 years, this disease is projected to be a
1 trillion dollar burden to the healthcare system. While imaging of fibrosis is somewhat diagnostic of NASH
progression, there is no metabolic imaging technique that is sensitive to the inflammation endemic to the
transition of NAFLD to NASH. Current stepwise paradigms for identifying NASH lack the sensitivity to correctly
classify early development. When NASH is diagnosed, clinical management of the disease changes
dramatically, becoming much more expensive. Development of a metabolic imaging method for diagnosis and
staging of NASH would significantly enhance healthcare practice, with prospects for improving patient care and
decreasing costs.

## Key facts

- **NIH application ID:** 10590690
- **Project number:** 5R01DK132254-02
- **Recipient organization:** UNIVERSITY OF FLORIDA
- **Principal Investigator:** MATTHEW E MERRITT
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $518,154
- **Award type:** 5
- **Project period:** 2022-04-01 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10590690

## Citation

> US National Institutes of Health, RePORTER application 10590690, Imaging Hepatic Energy Metabolism in NAFLD/NASH (5R01DK132254-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10590690. Licensed CC0.

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