Low-density lipoprotein receptor-related protein-1 dysfunction synergizes with dietary cholesterol to accelerate steatohepatitis progression

The Journal of Biological Chemistry
Allyson N HamlinDavid Y Hui

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

Apr 18, 1998·Gastroenterology·C P Day, O F James
Sep 5, 2006·Cell Metabolism·Montserrat MaríCarmen García-Ruiz
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
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
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
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
Dec 23, 2016·Gastroenterology·Sachin H PatelDean Yimlamai

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Citations

Aug 28, 2020·Frontiers in Physiology·Ekta PandeyEdward N Harris
Dec 19, 2019·Journal of Hepatology·Younis HazariGuido Kroemer
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

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