@article{4fabde412c0d438e8cac5448d00666fd,
title = "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",
abstract = "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 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.",
keywords = "eNOS, metformin, MRI, NAFLD, thin-layer chromatography",
author = "Bego{\~n}a Lavin and Eykyn, {Thomas R.} and Alkystis Phinikaridou and Aline Xavier and Shravan Kumar and Xabier Buqu{\'e} and Patricia Aspichueta and Carlos Sing-Long and Marco Arrese and Botnar, {Ren{\'e} M.} and Andia, {Marcelo E.}",
note = "Funding Information: This work was supported by (1) EPSRC (EP/P001009/1 and EP/P007619/1); (2) the British Heart Foundation (RG/12/1/29262); (3) the Centre of Excellence in Medical Engineering funded by the Wellcome Trust and EPSRC (203148/Z/16/Z); (4) FONDECYT 1211643 (to C.S‐L.), 1191145 (to M.A.), and 1220922 (to M.E.A.). (5) This publication has received funding from ANID through the Millennium Science Initiative Program – ICN2021_004, ANID ACE 210009 grant; (6) the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy's & St Thomas' NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health. (7) “Ayudas para apoyar grupos de investigaci{\'o}n del sistema Universitario Vasco” IT1476‐22 and (8) MCIU/AEI/FEDER, UE (PID2021‐124425OB‐I00). Publisher Copyright: {\textcopyright} 2023 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.",
year = "2023",
month = aug,
doi = "10.1002/nbm.4932",
language = "English",
volume = "36",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley and sons",
number = "8",
}