Intrahepatic cholesterol influences progression, inhibition and reversal of non-alcoholic steatohepatitis in hyperlipidemic mice

FEBS Letters
Kristiaan WoutersRonit Shiri-Sverdlov

Abstract

Hepatic inflammation is the key factor in non-alcoholic steatohepatitis (NASH) and promotes progression to liver damage. We recently identified dietary cholesterol as the cause of hepatic inflammation in hyperlipidemic mice. We now show that hepatic transcriptome responses are strongly dependent on cholesterol metabolism during diet-induced NASH and its inhibition by fenofibrate. Furthermore, we show that, despite doubling hepatic steatosis, pharmacological LXR activation reverses hepatic inflammation, in parallel with reversing hepatic cholesterol levels. Together, the results indicate a prominent role of cholesterol during the development, inhibition and reversal of hepatic inflammation in NASH and reveal potential new therapeutic strategies against NASH.

References

Apr 29, 1997·Proceedings of the National Academy of Sciences of the United States of America·S A KliewerJ M Lehmann
Apr 18, 1998·Gastroenterology·C P Day, O F James
Jul 15, 1999·Biochemical and Biophysical Research Communications·K MurakamiT Kadowaki
Oct 26, 1999·Endocrine Reviews·B Desvergne, W Wahli
Jan 16, 2002·The Journal of Biological Chemistry·Sean B JosephPeter Tontonoz
Jul 2, 2002·Journal of Lipid Research·Dieter LütjohannThomas A Bayer
Oct 12, 2004·Annual Review of Cell and Developmental Biology·Antonio Castrillo, Peter Tontonoz
Apr 9, 2005·Molecular Pharmacology·Martin G BelinskyGary D Kruh
Jun 9, 2005·American Journal of Physiology. Endocrinology and Metabolism·Aldo GrefhorstFolkert Kuipers
Jan 18, 2006·Cell·Joseph L GoldsteinMichael S Brown
Feb 10, 2006·Journal of Hepatology·Ronit Shiri-SverdlovMarten H Hofker
May 20, 2006·Current Medical Research and Opinion·Vasilios G AthyrosMoses S Elisaf
Sep 5, 2006·Cell Metabolism·Montserrat MaríCarmen García-Ruiz
May 4, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kanji YamaguchiAnna Mae Diehl
Jul 27, 2007·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Puneet PuriArun J Sanyal
Aug 11, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Anna Kotronen, Hannele Yki-Järvinen
Feb 12, 2008·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·C Fernández-MirandaJ A Solís-Herruzo
Jul 31, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kristiaan WoutersMarten H Hofker
Feb 24, 2009·Journal of Hepatology·Francisco CaballeroCarmen García-Ruiz

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Citations

Dec 7, 2010·Antioxidants & Redox Signaling·Christopher L GentileMichael J Pagliassotti
Oct 12, 2011·Current Opinion in Lipidology·Giovanni MussoRoberto Gambino
Jun 2, 2011·Journal of Pediatric Gastroenterology and Nutrition·Samar H IbrahimGregory J Gores
Aug 23, 2012·Journal of Gastroenterology and Hepatology·George N Ioannou
Oct 13, 2010·World Journal of Gastroenterology : WJG·Giovanni TarantinoAnnamaria Colao
May 10, 2012·Gut and Liver·Geoffrey C FarrellShivrakumar Chitturi
Feb 19, 2013·Journal of Lipid Research·George N IoannouChristopher Savard
Sep 5, 2013·Free Radical Research·G ServiddioG Vendemiale
Aug 19, 2015·The Proceedings of the Nutrition Society·Donald B JumpKelli A Lytle
Dec 26, 2015·Trends in Endocrinology and Metabolism : TEM·George N Ioannou
Dec 5, 2012·Progress in Lipid Research·Giovanni MussoMaurizio Cassader
Jul 14, 2012·Molecular and Cellular Endocrinology·Michele VaccaAntonio Moschetta
Nov 8, 2011·Biochimica Et Biophysica Acta·Anne TailleuxBart Staels
Sep 21, 2011·Atherosclerosis·Veerle BieghsRonit Shiri-Sverdlov
Jan 20, 2012·Journal of Digestive Diseases·Yuan LiuXiong Ma
Jun 2, 2015·Biochimica Et Biophysica Acta·Graciela ArguelloSilvana Zanlungo
Jan 13, 2015·The Journal of Nutritional Biochemistry·Jamie E MellsFrank A Anania
Apr 14, 2015·Gastroenterology Research and Practice·S GittoP Andreone
Jul 19, 2014·Bioscience, Biotechnology, and Biochemistry·Byeong Tak JeonGu Seob Roh
Apr 14, 2017·Journal of Lipid Research·George N IoannouChristopher Savard
Jun 8, 2017·Children·Francesco Massimo PerlaCaterina Anania
Oct 10, 2018·Transplantation·Irene Pierantonelli, Gianluca Svegliati-Baroni
May 11, 2019·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Rashmi PathakSubramanyam N Murthy
Aug 3, 2018·Journal of Translational Medicine·Erik TaylorJames Hamilton
Jul 22, 2019·Molecular Nutrition & Food Research·Antwi-Boasiako OtengSander Kersten
Feb 13, 2020·Biomedicines·Yvonne Oligschlaeger, Ronit Shiri-Sverdlov
Jun 5, 2020·Endocrinology·Maud VoisinMichael J Garabedian
May 5, 2012·American Journal of Physiology. Gastrointestinal and Liver Physiology·Geoffrey C Farrell, Derrick van Rooyen
Jan 24, 2019·Cell Reports·Natalia BecaresInés Pineda-Torra
Feb 6, 2021·Cellular and Molecular Gastroenterology and Hepatology·Marica CarielloAntonio Moschetta
Jun 30, 2021·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Chu-Tian MaiYing Xie

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