Detecting altered hepatic lipid oxidation by MRI in an animal model of NAFLD

Abstract

Nonalcoholic fatty liver disease (NAFLD) prevalence is increasing annually and affects over a third of U.S. adults. NAFLD can progress to nonalcoholic steatohepatitis (NASH), characterized by severe inflammation and fibrosis. NASH is predicted to become the primary cause of liver transplant by 2030. Although the etiology of NAFLD/NASH is incompletely understood, dysregulated fatty acid oxidation is implicated in disease pathogenesis. Here, we developed a method for estimating hepatic {beta}-oxidation from the metabolism of [D15]octanoate to deuterated water and detection with deuterium magnetic resonance methods. Application of this method to perfused liver from a mouse model of NAFLD revealed dysregulated hepatic {beta}-oxidation, findings that we confirmed with in vivo imaging. The high-fat diet-induced NAFLD mouse studies indicated that decreased {beta}-oxidative efficiency in the fatty liver could serve as a prognostic indicator of NAFLD progression. Furthermore, our method provides a clinically translatable imaging approach for determining hepatic {beta}-oxidation efficiency.