| ISSN |
1007-9327 (print) and 2219-2840 (online) |
| Open Access |
This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/ |
| Copyright |
© The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved. |
| Article Reprints |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/247
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| Permissions |
For details, please visit: http://www.wjgnet.com/bpg/gerinfo/207
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| Publisher |
Baishideng Publishing Group Inc, 7041 Koll Center Parkway, Suite 160, Pleasanton, CA 94566, USA |
| Website |
http://www.wjgnet.com |
| Category |
Gastroenterology & Hepatology |
| Manuscript Type |
Basic Study |
| Article Title |
Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation
|
| Manuscript Source |
Unsolicited Manuscript |
| All Author List |
David Fernández-Ramos, Fernando Lopitz-Otsoa, Laura Delacruz-Villar, Jon Bilbao, Martina Pagano, Laura Mosca, Maider Bizkarguenaga, Marina Serrano-Macia, Mikel Azkargorta, Marta Iruarrizaga-Lejarreta, Jesús Sot, Darya Tsvirkun, Sebastiaan Martijn van Liempd, Felix M Goni, Cristina Alonso, María Luz Martínez-Chantar, Felix Elortza, Liat Hayardeny, Shelly C Lu and José M Mato |
| ORCID |
|
| Funding Agency and Grant Number |
| Funding Agency |
Grant Number |
| National Institutes of Health Grant |
R01CA172086 |
| Plan Nacional of I+D |
SAF2017-87301-R |
| Ministerio de Economía y Competitividad de España |
SAF2017-87301-R |
| Asociación Española contra el Cáncer |
AECC17/302 |
| Ayudas Fundación BBVA a equipos de Investigación Científica 2018 |
|
| Fondo Europeo de Desarrollo Regional, Ministerio de Economia y Competitividad de España, |
PGC2018-099857-B-I00 |
| Basque Government Grants |
IT1264-19 |
| Ministerio de Economia y Competitividad de España for the Severo Ochoa Excellence Accreditation |
SEV-2016-0644 |
|
| Corresponding Author |
José M Mato, PhD, Director, Professor, Precision Medicine and Metabolism Laboratory, Centro de Investigación Cooperativa en Biociencias, Parque Tecnológico de Bizkaia, Derio 48160, Bizkaia, Spain. director@cicbiogune.es |
| Key Words |
Nonalcoholic fatty liver disease; Steatohepatitis; Methionine and choline deficient diet; Tricarboxylic acid cycle; Hemoglobin A1c; Stearoyl-CoA desaturase 1 |
| Core Tip |
Arachidyl amido cholanoic acid (Aramchol), a phase III investigational drug for the treatment of nonalcoholic steatohepatitis (NASH), has demonstrated reduction of liver steatosis, inflammation and fibrosis in various animal models of steatohepatitis. In a phase IIb clinical trial, it reduced blood levels of glycated hemoglobin A1c, an indicator of glycemic control. In this study, we show that Aramchol-treated hepatocytes activate AMPK and inhibit mTORC1, which in turn activate fatty acid β-oxidation and oxidative phosphorylation inhibiting de novo lipogenesis, gluconeogenesis and cataplerosis. These results explain the mechanism by which Aramchol exerts its effect on glucose and lipid metabolism in NASH. |
| Publish Date |
2020-09-09 11:11 |
| Citation |
Fernández-Ramos D, Lopitz-Otsoa F, Delacruz-Villar L, Bilbao J, Pagano M, Mosca L, Bizkarguenaga M, Serrano-Macia M, Azkargorta M, Iruarrizaga-Lejarreta M, Sot J, Tsvirkun D, van Liempd SM, Goni FM, Alonso C, Martínez-Chantar ML, Elortza F, Hayardeny L, Lu SC, Mato JM. Arachidyl amido cholanoic acid improves liver glucose and lipid homeostasis in nonalcoholic steatohepatitis via AMPK and mTOR regulation. World J Gastroenterol 2020; 26(34): 5101-5117 |
| URL |
https://www.wjgnet.com/1007-9327/full/v26/i34/5101.htm |
| DOI |
https://dx.doi.org/10.3748/wjg.v26.i34.5101 |
