Characterization of hepatic fatty acids using magnetic resonance spectroscopy for the assessment of treatment response to metformin in an eNOS(-/-) mouse model of metabolic nonalcoholic fatty liver disease/nonalcoholic steatohepatitis

Lavin, Begona; Eykyn, Thomas R.; Phinikaridou, Alkystis; Xavier, Aline; Kumar, Shravan; Buque, Xabier; Aspichueta, Patricia; Sing-Long, Carlos; Arrese, Marco; Botnar, Rene M.; Andia, Marcelo E.


Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Liver biopsy remains the gold standard for diagnosis and staging of disease. There is a clinical need for noninvasive diagnostic tools for risk stratification, follow-up, and monitoring treatment response that are currently lacking, as well as preclinical models that recapitulate the etiology of the human condition. We have characterized the progression of NAFLD in eNOS(-/-) mice fed a high fat diet (HFD) using noninvasive Dixon-based magnetic resonance imaging and single voxel STEAM spectroscopy-based protocols to measure liver fat fraction at 3 T. After 8 weeks of diet intervention, eNOS(-/-) mice exhibited significant accumulation of intra-abdominal and liver fat compared with control mice. Liver fat fraction measured by H-1-MRS in vivo showed a good correlation with the NAFLD activity score measured by histology. Treatment of HFD-fed NOS3(-/-) mice with metformin showed significantly reduced liver fat fraction and altered hepatic lipidomic profile compared with untreated mice. Our results show the potential of in vivo liver MRI and H-1-MRS to noninvasively diagnose and stage the progression of NAFLD and to monitor treatment response in an eNOS(-/-) murine model that represents the classic NAFLD phenotype associated with metabolic syndrome.

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Título según WOS: ID WOS:000969102500001 Not found in local WOS DB
Título de la Revista: NMR IN BIOMEDICINE
Editorial: Wiley
Fecha de publicación: 2023


Notas: ISI