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

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.