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Assessment of hepatic fatty acids during non-alcoholic steatohepatitis progression using magnetic resonance spectroscopy

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Aline Xavier, Flavia Zacconi, Fabián Santana-Romo, Thomas R. Eykyn, Begoña Lavin, Alkystis Phinikaridou, René Botnar, Sergio Uribe, Juan Esteban Oyarzún, Daniel Cabrera, Marco Arrese, Marcelo E. Andia

Original languageEnglish
Article number100358
JournalAnnals Of Hepatology
Volume25
DOIs
Published1 Nov 2021

Bibliographical note

Funding Information: This work was partially funded by ANID ? Millennium Science Initiative Program ? NCN17_129. FONDECYT 1180525, 11171001, 1211879, 1191145 to MEA, DC, DC and MA, respectively. CONICYT-PCHA/Doctorado Nacional /2016-21160835. This work was also funded, in part, by grants the Comisi?n Nacional de Investigaci?n, Ciencia y Tecnolog?a (CONICYT, AFB170005, CARE Chile UC). The Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC (203148/Z/16/Z). MA is part of the European-Latin American ESCALON consortium funded by the European Union's Horizon 2020 Research and Innovation Program under grant agreement no. 825510. FZ is grateful to FONDEQUIP EQM120021 and EQM150020 from Pontificia Universidad Cat?lica de Chile. FS-R, AX, and FZ thank ChemAxon for MarvinSketch software for chemical drawing, displaying, and characterizing chemical structures, substructures, and reactions, Marvin 18.27.0 (https://www.chemaxon.com); Instant JChem was used for structure database management, search, and prediction, Instant JChem 18.26.0, ChemAxon (http://www.chemaxon.com). Abstract figure created with BioRender.com. Funding Information: This work was partially funded by ANID – Millennium Science Initiative Program – NCN17_129 . FONDECYT 1180525 , 11171001 , 1211879 , 1191145 to MEA, DC, DC and MA, respectively. CONICYT-PCHA/Doctorado Nacional / 2016-21160835 . This work was also funded, in part, by grants the Comisión Nacional de Investigación , Ciencia y Tecnología (CONICYT, AFB170005 , CARE Chile UC). The Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC ( 203148/Z/16/Z ). MA is part of the European-Latin American ESCALON consortium funded by the European Union's Horizon 2020 Research and Innovation Program under grant agreement no. 825510 . Publisher Copyright: © 2021 Fundación Clínica Médica Sur, A.C. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.

King's Authors

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.

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