Detecting altered hepatic lipid oxidation by MRI in an animal model of MASLD
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 [D<sub>15</sub>]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.
Authors
- Matthew E. Merritt (ORCID: https://orcid.org/0000-0003-4617-9651)
- Anna Rushin (ORCID: https://orcid.org/0000-0002-5643-0101)
- Mario C. Chang (ORCID: https://orcid.org/0000-0002-2452-2693)
- Anthony Giacalone
- Nishanth E. Sunny (ORCID: https://orcid.org/0000-0003-1607-2095)
- Gaurav Sharma (ORCID: https://orcid.org/0000-0002-5296-558X)
- Rohit Mahar (ORCID: https://orcid.org/0000-0002-9801-4173)
- Mukundan Ragavan (ORCID: https://orcid.org/0000-0001-8678-4229)
- James A. Bankson (ORCID: https://orcid.org/0000-0002-8574-154X)
- Vinay Malut (ORCID: https://orcid.org/0009-0005-1006-6323)
- Kenneth Cusi (ORCID: https://orcid.org/0000-0002-8629-418X)
- Marc McLeod (ORCID: https://orcid.org/0009-0004-5193-3529)
- Dalton Graham
- Arshee Badar
- Max Glanz (ORCID: https://orcid.org/0009-0007-9724-478X)
Institutions
- St. Jude Children's Research Hospital (US)
- The University of Texas MD Anderson Cancer Center (US)
- Hemwati Nandan Bahuguna Garhwal University (IN)
- University of Florida Health (US)
- University of Florida (US)
- University of Maryland, College Park (US)
- The University of Texas Southwestern Medical Center (US)
- Florida College (US)
Publication Details
- Journal
- Cell Reports Medicine
- Published
- 2024-09-01
- DOI
- https://doi.org/10.1016/j.xcrm.2024.101714
- Citations
- 6
- Primary Topic
- Liver Disease Diagnosis and Treatment
- Type
- article
- Field-Weighted Citation Impact
- 2.32
Funders
- National Science Foundation
- McKnight Foundation
- National High Magnetic Field Laboratory
- National Institutes of Health
- Division of Materials Research
- High Magnetic Field Laboratory, Chinese Academy of Sciences