Detection of early-stage NASH using non-invasive hyperpolarized 13C metabolic imaging.
Sci Rep
; 14(1): 14854, 2024 06 27.
Article
em En
| MEDLINE
| ID: mdl-38937567
ABSTRACT
Non-alcoholic steatohepatitis (NASH) is characterized from its early stages by a profound remodeling of the liver microenvironment, encompassing changes in the composition and activities of multiple cell types and associated gene expression patterns. Hyperpolarized (HP) 13C MRI provides a unique view of the metabolic microenvironment, with potential relevance for early diagnosis of liver disease. Previous studies have detected changes in HP 13C pyruvate to lactate conversion, catalyzed by lactate dehydrogenase (LDH), with experimental liver injury. HP â -ketobutyrate ( â KB) is a close molecular analog of pyruvate with modified specificity for LDH isoforms, specifically attenuated activity with their LDHA-expressed subunits that dominate liver parenchyma. Building on recent results with pyruvate, we investigated HP â KB in methionine-choline deficient (MCD) diet as a model of early-stage NASH. Similarity of results between this new agent and pyruvate (~ 50% drop in cytoplasmic reducing capacity), interpreted together with gene expression data from the model, suggests that changes are mediated through broad effects on intermediary metabolism. Plausible mechanisms are depletion of the lactate pool by upregulation of gluconeogenesis (GNG) and pentose phosphate pathway (PPP) flux, and a possible shift toward increased lactate oxidation. These changes may reflect high levels of oxidative stress and/or shifting macrophage populations in NASH.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Isótopos de Carbono
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Imageamento por Ressonância Magnética
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Hepatopatia Gordurosa não Alcoólica
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article