Adaptive failure to high-fat diet characterizes steatohepatitis in Alms1 mutant mice

Biochemical and Biophysical Research Communications
Todor ArsovGeoffrey C Farrell

Abstract

The biochemical differences between simple steatosis, a benign liver disease, and non-alcoholic steatohepatitis, which leads to cirrhosis, are unclear. Fat aussie is an obese mouse strain with a truncating mutation (foz) in the Alms1 gene. Chow-fed female foz/foz mice develop obesity, diabetes, and simple steatosis. We fed foz/foz and wildtype mice a high-fat diet. Foz/foz mice developed serum ALT elevation and severe steatohepatitis with hepatocyte ballooning, inflammation, and fibrosis; wildtype mice showed simple steatosis. Biochemical pathways favoring hepatocellular lipid accumulation (fatty acid uptake; lipogenesis) and lipid disposal (fatty acid beta-oxidation; triglyceride egress) were both induced by high-fat feeding in wildtype but not foz/foz mice. The resulting extremely high hepatic triglyceride levels were associated with induction of mitochondrial uncoupling protein-2 and adipocyte-specific fatty acid binding protein-2, but not cytochrome P4502e1 or lipid peroxidation. In this model of metabolic syndrome, transition of steatosis to steatohepatitis was associated with hypoadiponectinemia, a mediator of hepatic fatty acid disposal pathways.

References

Jun 1, 1996·The Journal of Clinical Investigation·A Vidal-PuigD E Moller
Apr 18, 1998·Gastroenterology·C P Day, O F James
Sep 17, 1999·Journal of Hepatology·S H CaldwellW D Parker
Nov 26, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·P AnguloK D Lindor
Apr 20, 2000·The Journal of Clinical Investigation·I A LeclercqG R Robertson
Apr 26, 2001·Proceedings of the National Academy of Sciences of the United States of America·S C LuJ M Mato
Dec 12, 2001·The Journal of Biological Chemistry·Johan BjörkegrenStephen G Young
Mar 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Michael CharltonK Sreekumaran Nair
Apr 19, 2002·The New England Journal of Medicine·Paul Angulo
Jul 27, 2002·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Amedeo Lonardo, Paola Loria
Aug 31, 2002·Journal of Gastroenterology and Hepatology·Katsuhisa OmagariShigeru Kohno
Apr 2, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giovanni MussoGianfranco Pagano
Jun 13, 2003·Nature·Toshimasa YamauchiTakashi Kadowaki
Jul 4, 2003·The Journal of Clinical Investigation·Aimin XuGarth J S Cooper
Oct 11, 2003·Journal of Gastroenterology and Hepatology·Richard KirschPauline de la M Hall
Jul 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jason M HuiJacob George
Jul 9, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Takayuki MasakiHironobu Yoshimatsu
Jul 16, 2004·The Journal of Clinical Investigation·Jeffrey D Browning, Jay D Horton
Sep 24, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Tamie NakajimaToshifumi Aoyama
Nov 27, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Jeffrey D BrowningHelen H Hobbs
Jan 22, 2005·Science·Bradford B Lowell, Gerald I Shulman
May 3, 2005·The Journal of Clinical Investigation·Shinji Tamura, Iichiro Shimomura
May 26, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·David E KleinerUNKNOWN Nonalcoholic Steatohepatitis Clinical Research Network
Jun 3, 2005·Current Diabetes Reports·Rebecca Parish, Kitt Falk Petersen
Aug 20, 2005·Diabetic Medicine : a Journal of the British Diabetic Association·S JimbaT Wasada
Aug 24, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Frank A Anania
Sep 22, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qing-Gao DengHidekazu Tsukamoto

❮ Previous
Next ❯

Citations

Apr 29, 2010·Current Gastroenterology Reports·Brent A Neuschwander-Tetri
Jan 24, 2009·The British Journal of Nutrition·Florence M SohetNathalie M Delzenne
Mar 10, 2011·International Journal of Obesity : Journal of the International Association for the Study of Obesity·K S Bell-AndersonI D Caterson
Oct 18, 2007·European Journal of Human Genetics : EJHG·Jan D MarshallJürgen K Naggert
Dec 4, 2010·Antioxidants & Redox Signaling·Jacquelyn J Maher
Jul 5, 2007·Journal of Gastroenterology and Hepatology·Shivakumar Chitturi, Geoffrey C Farrell
Aug 30, 2008·Journal of Gastroenterology and Hepatology·Claire Z Larter, Matthew M Yeh
Aug 4, 2009·Journal of Gastroenterology and Hepatology·Christopher J Nolan, Claire Z Larter
Oct 1, 2009·Journal of Gastroenterology and Hepatology·Claire Z LarterGeoffrey C Farrell
Oct 14, 2009·Journal of Gastroenterology and Hepatology·Geoffrey C Farrell
May 25, 2010·Journal of Gastroenterology and Hepatology·Claire Z LarterGeoffrey C Farrell
Jan 12, 2010·Annual Review of Medicine·Giovanni MussoMaurizio Cassader
Aug 13, 2011·American Journal of Physiology. Gastrointestinal and Liver Physiology·Michael CharltonGregory Gores
Feb 14, 2012·Journal of Lipid Research·Elizabeth P NewberryNicholas O Davidson
May 9, 2012·Disease Models & Mechanisms·Dominic P Norris, Daniel T Grimes
Nov 7, 2013·International Journal of Molecular Sciences·Kento ImajoAtsushi Nakajima
Jun 2, 2012·World Journal of Gastroenterology : WJG·Yoshihisa TakahashiToshio Fukusato
May 10, 2012·Gut and Liver·Geoffrey C FarrellShivrakumar Chitturi
Dec 17, 2015·Annual Review of Physiology·Joel T HaasBart Staels
Jun 28, 2011·Gastroenterology·Derrick M Van RooyenGeoffrey C Farrell
Feb 19, 2009·Digestive and Liver Disease : Official Journal of the Italian Society of Gastroenterology and the Italian Association for the Study of the Liver·S PettaA Craxì
Oct 28, 2008·Toxicology and Applied Pharmacology·Maxwell Afari GyamfiYu-Jui Yvonne Wan
Jun 5, 2007·Clinics in Liver Disease·Roslyn M London, Jacob George
Dec 24, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giovanni MussoMaurizio Cassader
Mar 4, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giovanni MussoMaurizio Cassader
Jun 12, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Giovanni MussoRoberto Gambino
Mar 17, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Gavin E Arteel
Aug 5, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Brent A Neuschwander-Tetri
Feb 5, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Narci C TeohGeoffrey C Farrell
Apr 12, 2016·Alimentary Pharmacology & Therapeutics·M NoureddinR Loomba
Jun 7, 2015·Archives of Toxicology·Sara Crespo YanguasMathieu Vinken
Feb 19, 2008·Journal of Hepatology·Claire Z LarterGeoffrey C Farrell
Jul 24, 2013·Seminars in Cancer Biology·Jun YuNathalie Wong
Apr 19, 2011·Best Practice & Research. Clinical Gastroenterology·Peter Starkel, I A Leclercq
Nov 6, 2014·Oxidative Medicine and Cellular Longevity·Aaron M GusdonShen Qu
May 15, 2016·Liver International : Official Journal of the International Association for the Study of the Liver·Laura L GathercoleTarekegn Geberhiwot
Mar 1, 2017·Journal of Lipid Research·Giovanni MussoRoberto Gambino
Sep 18, 2015·Cells·Nathalie FalkAndreas Gießl

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE, Lipids & Cholesterol

Serum cholesterol, triglycerides, apolipoprotein B (APOB)-containing lipoproteins (very low-density lipoprotein (VLDL), immediate-density lipoprotein (IDL), and low-density lipoprotein (LDL), lipoprotein A (LPA)) and the total cholesterol/high-density lipoprotein (HDL) cholesterol ratio are all connected in diseases. Here is the latest research.

Alstrom Syndrome

Alstrom syndrome is a rare disorder characterized by early obesity, loss of central vision, diabetes mellitus, hearing loss, and short stature. Here is the latest research.

Related Papers

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Qing-Gao DengHidekazu Tsukamoto
Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Giovanni MussoGianfranco Pagano
Digestive Diseases and Sciences
Steven SolgaThomas Magnuson
© 2021 Meta ULC. All rights reserved