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Abstract #4918

In vivo Imaging of Dysregulated β-Oxidation in a Diet-Induced Model of MASLD with [D15]octanoate

Mario C. Chang1, Marc McLeod2, Anna Rushin1, Mukundan Ragavan1,3, Rohit Mahar4, Gaurav Sharma1, Arshee Badar1, Anthony Giacalone1, Max E. Glanz1, Vinay R. Malut1, Dalton Graham1, Nishanth E. Sunny5, James A. Bankson6, Kenneth Cusi7, and Matthew E. Merritt1
1Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, United States, 2University of Texas Southwestern Medical Center, Dallas, TX, United States, 3Structural Biology, St. Jude Children's Research Hospital, Memphis, TN, United States, 4Chemistry, Hemvati Nandan Bahuguna Garhwal University (A Central University), Srinagar Garhwal, India, 5Animal and Avian Sciences, University of Maryland, College Park, MD, United States, 6Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX, United States, 7Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, Veterans Health Administration, University of Florida, Gainesville, FL, United States

Synopsis

Keywords: Biology, Models, Methods, Metabolism

Motivation: Metabolic dysfunction-associated steatotic liver disease (MASLD) affects more than 30% of adults in the US. Disease can progress to more severe forms and eventually death. Current diagnosis by liver biopsy is limited by sampling error and morbidity risk. Development of improved diagnostics is required.

Goal(s): Development of a minimally invasive method based on deuterium metabolic imaging (DMI) may improve MASLD diagnostics.

Approach: Imaging deuterated water (HDO) production from [D15]octanoate metabolism to assess β-oxidative capacity in a MASLD mouse model.

Results: [D15]octanoate DMI generated metabolic maps of β-oxidation and demonstrated reduced β-oxidative efficiency that correlated with clinically relevant assays for MASLD.

Impact: Imaging HDO production from [D15]octanoate oxidation can detect organ specific metabolism and may lead to a novel clinical method for staging MASLD in a minimally invasive manner. [D15]octanoate DMI needs to be tested in humans to assess clinical capability.

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Abstract

Keywords