Abstract
Reduced low-density lipoprotein receptor-related protein-1 (LRP1) expression in the liver is associated with poor prognosis of liver cirrhosis and hepatocellular carcinoma. Previous studies have shown that hepatic LRP1 deficiency exacerbates palmitate-induced steatosis and toxicity in vitro and also promotes high-fat diet-induced hepatic insulin resistance and hepatic steatosis in vivo The current study examined the impact of liver-specific LRP1 deficiency on disease progression to steatohepatitis. hLrp1+/+ mice with normal LRP1 expression and hLrp1-/- mice with hepatocyte-specific LRP1 inactivation were fed a high-fat, high-cholesterol (HFHC) diet for 16 weeks. Plasma lipid levels and body weights were similar between both groups. However, the hLrp1-/- mice displayed significant increases in liver steatosis, inflammation, and fibrosis compared with the hLrp1+/+ mice. Hepatocyte cell size, liver weight, and cell death, as measured by serum alanine aminotransferase levels, were also significantly increased in hLrp1-/- mice. The accelerated liver pathology observed in HFHC-fed hLrp1-/- mice was associated with reduced expression of cholesterol excretion and bile acid synthesis genes, leading to elevated immune cell infiltration a...Continue Reading
References
Mar 21, 1998·The Journal of Clinical Investigation·A RohlmannJ Herz
Apr 18, 1998·Gastroenterology·C P Day, O F James
Sep 5, 2006·Cell Metabolism·Montserrat MaríCarmen García-Ruiz
Apr 26, 2007·Annals of Medicine·Petra MayPhilippe Boucher
Oct 20, 2007·The Journal of Clinical Investigation·Susanna M HofmannDavid Y Hui
Jul 16, 2008·Physiological Reviews·Anna P LillisDudley K Strickland
Jul 31, 2008·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Kristiaan WoutersMarten H Hofker
Sep 23, 2008·Biochimica Et Biophysica Acta·P StrnadH Denk
Nov 20, 2008·Journal of Lipid Research·Joachim HerzLi Zhou
May 15, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·George N IoannouSum P Lee
Jun 24, 2009·Digestive Diseases·Kerstin SchüttePeter Malfertheiner
Sep 1, 2009·PloS One·Li ZhouJoachim Herz
Aug 27, 2010·Journal of Hepatology·Manabu KinoshitaShuhji Seki
Feb 24, 2011·The Journal of Biological Chemistry·Joshua E BasfordDavid Y Hui
Apr 5, 2011·Autophagy·Jeffrey HaspelAugustine M K Choi
Apr 30, 2011·Clinical Medicine : Journal of the Royal College of Physicians of London·Christopher P Day
Jun 22, 2011·Journal of Lipid Research·Savitha SubramanianAlan Chait
Mar 20, 2012·PloS One·Xiao-Yong HuangJian Zhou
Apr 18, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Christopher SavardGeorge N Ioannou
May 10, 2012·Therapeutic Advances in Gastroenterology·Jacob M KneemanKathleen E Corey
May 6, 2016·Journal of Lipid Research·Jessica M FerrellJohn Y L Chiang
Jun 4, 2016·International Journal of Molecular Sciences·Mariana Verdelho Machado, Anna Mae Diehl
Jun 19, 2016·The Journal of Biological Chemistry·Allyson N HamlinDavid Y Hui
Jun 21, 2016·EBioMedicine·Yinyuan DingJoachim Herz
Dec 23, 2016·Gastroenterology·Sachin H PatelDean Yimlamai
Jan 4, 2017·EBioMedicine·Jun ZhangYang Li
Jan 10, 2017·Cell Metabolism·Xiaobo WangIra Tabas
Nov 17, 2017·ELife·Xunde XianJoachim Herz
Citations
Feb 11, 2020·Lipids·Neng Tanty SofyanaTatsuya Sugawara
Apr 25, 2019·Scientific Reports·Maya O TreeMichael J Conway
Aug 28, 2020·Frontiers in Physiology·Ekta PandeyEdward N Harris
Dec 11, 2020·Journal of Lipid Research·Anja JaeschkeDavid Y Hui
Dec 19, 2019·Journal of Hepatology·Younis HazariGuido Kroemer
Feb 7, 2021·The Journal of Biological Chemistry·Sivaprakasam ChinnarasuDavid Y Hui
Jan 28, 2021·Journal of Lipid Research·Anja JaeschkeDavid Y Hui
Oct 4, 2020·Molecular Metabolism·Audrey DeprinceBart Staels
Apr 24, 2021·Molecular Metabolism·Joerg Heeren, Ludger Scheja
Jul 27, 2021·Current Opinion in Lipidology·Anja Jaeschke, David Y Hui
Dec 11, 2020·CNS & Neurological Disorders Drug Targets·Ruchi Jakhmola-ManiDeepshikha Pande Katare