Evaluating hepatic metabolic derangements in a diet and oxidative stress induced mouse model of MASLD with hyperpolarized [1-13C]-pyruvate

Motivation: Clinical management of metabolic dysfunction-associated steatotic liver disease (MASLD) is hindered by the absence of non-invasive tests to longitudinally monitor disease progression and treatment response. Goal(s): Evaluate if hyperpolarized (HP) [1-13C]-pyruvate MRS can distinguish different grades of steatotic liver injury. Approach: In a mouse model of MASLD, ex vivo metabolite analysis was performed to characterized perturbations in pyruvate metabolism associated with disease progression. This was used to guide interpretation of in vivo HP MRS. Results: Ex vivo analysis demonstrates decreasing pyruvate dehydrogenase (PDH) flux relative to pyruvate carboxylase throughout disease progression. HP MRS demonstrates decreased PDH flux in early MASLD relative to control. Impact: Our results demonstrate that HP [1-13C]-pyruvate is a promising molecular imaging probe for the non-invasive diagnosis of simple steatosis/MASH and potentially offers a safe alternative to liver biopsy that is more appropriate for longitudinal disease monitoring.