# Coordination of hepatic fatty acid metabolism

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2020 · $409,375

## Abstract

The balance of hepatic lipid synthesis, uptake, export and oxidation plays an important role in the progression
and pathogenesis of the metabolic syndrome and is particularly important for the growing incidence of
Nonalcoholic Steatohepatitis (NASH). However, the mechanisms governing the shift from normal metabolic
physiology to pathophysiology are poorly understood, particularly with respect to the role of lipid metabolism.
Our overall goal is to determine how the liver senses and responds to fluctuations in fatty acid availability to
facilitate key processes such as gluconeogenesis and ketogenesis, and to understand how targeting lipid
metabolism could either protect or potentiate obesity, diabetes and NASH. We have developed multiple mouse
models that disrupt fatty acid catabolism at unique metabolic nodes in the liver. We have shown that although
all of these models exhibit fatty liver and exist in a putative linear pathway for the oxidation of fatty acids, they
exhibit surprisingly unique cellular and molecular phenotypes. These data demonstrate that both triglyceride
hydrolysis and fatty acid oxidation convey unique biochemical information to the hepatocyte to coordinate the
catabolism of fatty acids. To describe this unique fatty acid dependent regulatory code, we propose three
specific aims to 1) Determine the independent roles for triglyceride hydrolysis and fatty acid oxidation during
fasting, 2) Determine the independent and interdependent roles of triglyceride hydrolysis and fatty acid
oxidation in HFD-induced obesity and 3) Determine the role of fatty acid-dependent lysine acetylation in the
regulation of hepatic metabolism. Here we will use these models to understand the metabolic code by which
fatty acids affect the hepatic coordination of lipid metabolism.

## Key facts

- **NIH application ID:** 10116890
- **Project number:** 1R01DK120530-01A1
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Michael J. Wolfgang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $409,375
- **Award type:** 1
- **Project period:** 2020-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10116890

## Citation

> US National Institutes of Health, RePORTER application 10116890, Coordination of hepatic fatty acid metabolism (1R01DK120530-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10116890. Licensed CC0.

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