Browsing by Author "Xavier, Aline"
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- ItemAssessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy(2021) Xavier, Aline; Zacconi, Flavia C. M.; Santana Romo, Fabián Mauricio; Eykyn, Thomas R.; Lavin, Begona; Phinikaridou, Alkystis; Botnar, Rene; Uribe, Sergio; Esteban Oyarzun, Juan; Cabrera, Daniel; Arrese, Marco; Andia, Marcelo E.Abstract: Introduction and objectives: Non-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of liver abnormalities including steatosis, steatohepatitis, fibrosis, and cirrhosis. Liver biopsy remains the gold standard method to determine the disease stage in NAFLD but is an invasive and risky procedure. Studies have previously reported that changes in intrahepatic fatty acids (FA) composition are related to the progression of NAFLD, mainly in its early stages. The aim of this study was to characterize the liver FA composition in mice fed a Choline-deficient L-amino-defined (CDAA) diet at different stages of NAFLD using magnetic resonance spectroscopy (MRS). Methods: We used in-vivo MRS to perform a longitudinal characterization of hepatic FA changes in NAFLD mice for 10 weeks. We validated our findings with ex-vivo MRS, gas chromatography-mass spectrometry and histology. Results: In-vivo and ex-vivo results showed that livers from CDAA-fed mice exhibit a significant increase in liver FA content as well as a change in FA composition compared with control mice. After 4 weeks of CDAA diet, a decrease in polyunsaturated and an increase in monounsaturated FA were observed. These changes were associated with the appearance of early stages of steatohepatitis, confirmed by histology (NAFLD Activity Score (NAS) = 4.5). After 10 weeks of CDAA-diet, the liver FA composition remained stable while the NAS increased further to 6 showing a combination of early and late stages of steatohepatitis. Conclusion: Our results suggest that monitoring lipid composition in addition to total water/fat with MRS may yield additional insights that can be translated for non-invasive stratification of high-risk NAFLD patients.
- ItemCharacterization 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(2023) Lavin, Begoña; Eykyn, Thomas; Phinikaridou, Alkystis; Xavier, Aline; Kumar, Shravan; Buqué, Xabier; Aspichueta, Patricia; Sing-Long C., Carlos A.; Arrese, Marco; Botnar, René Michael; Andía Kohnenkampf, Marcelo EdgardoNonalcoholic 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 1H-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 1H-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.