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Updated: Jun 14, 2025
Author Spotlight: Establishing MASLD Cell Models for Investigating Disease Mechanisms and the Lipid-Lowering Effects of Koumiss
Published on: July 19, 2024
Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD
Marc McLeod1, Mario C Chang2, Anna Rushin2
1Department of Biochemistry and Molecular Biology, University of Florida College of Medicine, Gainesville, FL 32610, USA; University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9014, USA.
Abstract:
Metabolic dysfunction-associated steatotic liver disease (MASLD) prevalence is increasing annually and affects over a third of US adults. MASLD can progress to metabolic dysfunction-associated steatohepatitis (MASH), characterized by severe hepatocyte injury, inflammation, and eventual advanced fibrosis or cirrhosis. MASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of MASLD/MASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we develop a method for estimating hepatic β-oxidation from the metabolism of [D15]octanoate to deuterated water and detection with deuterium magnetic resonance methods. Perfused livers from a mouse model of MASLD reveal dysregulated hepatic β-oxidation, findings that corroborate in vivo imaging. The high-fat-diet-induced MASLD mouse studies indicate that decreased β-oxidative efficiency in the fatty liver could serve as an indicator of MASLD progression. Furthermore, our method provides a clinically translatable imaging approach for determining hepatic β-oxidation efficiency.
Insights
A new method estimates fatty liver disease (MASLD) progression by measuring hepatic beta-oxidation. Decreased beta-oxidation efficiency in fatty liver may indicate disease advancement, aiding clinical diagnosis.
Area of Science:
- Hepatology
- Metabolic Diseases
- Biochemistry
Background:
- Metabolic dysfunction-associated steatotic liver disease (MASLD) affects over a third of US adults and can progress to metabolic dysfunction-associated steatohepatitis (MASH).
- MASH is a leading cause of liver transplantation, driven by hepatocyte injury, inflammation, and fibrosis.
- Dysregulated fatty acid oxidation is a key factor in MASLD/MASH pathogenesis.
Purpose of the Study:
- To develop a novel method for quantifying hepatic beta-oxidation.
- To assess hepatic beta-oxidation in a mouse model of MASLD.
- To establish a clinically translatable imaging approach for evaluating liver fat metabolism.
Main Methods:
- Utilized [D15]octanoate metabolism to deuterated water for hepatic beta-oxidation estimation.
- Employed deuterium magnetic resonance methods for detection.
- Studied perfused livers from a high-fat-diet-induced MASLD mouse model.
Main Results:
- Demonstrated dysregulated hepatic beta-oxidation in MASLD mouse livers.
- Corroborated findings with in vivo imaging.
- Identified decreased beta-oxidative efficiency as a potential indicator of MASLD progression.
Conclusions:
- The developed method accurately estimates hepatic beta-oxidation.
- Reduced beta-oxidative efficiency is linked to MASLD progression.
- This technique offers a clinically translatable imaging tool for MASLD assessment.
