Abstract
The objectives of this analysis are to re-examine the foundational studies of the in vivo metabolism of plasma LDL (low-density lipoprotein) particles in humans and, based on them, to reconstruct our understanding of the governance of the concentration of plasma LDL and the maintenance of cholesterol homoeostasis in the hepatocyte. We believe that regulation of cholesterol homoeostasis within the hepatocyte is demonstrably more complex than envisioned by the LDL receptor paradigm, the conventional model to explain the regulation of plasma LDL and the fluxes of cholesterol into the liver, a model which was generated in the fibroblast but has never been fully validated in the hepatocyte. We suggest that the LDL receptor paradigm should be reconfigured as the apoB (apolipoprotein B) paradigm, which states that the rate at which LDL particles are produced is at least an important determinant of their concentration in plasma as the rate at which they are cleared from plasma and that secretion of cholesterol within VLDL (very-low-density lipoprotein) particles is an important mechanism of maintaining cholesterol homoeostasis within the hepatocyte. These two paradigms are not mutually exclusive. The LDL receptor paradigm, however, inc...Continue Reading
References
Aug 1, 1979·The Journal of Clinical Investigation·D W BilheimerS M Grundy
Nov 1, 1987·The Biochemical Journal·L M HavekesH M Princen
Apr 4, 1986·Science·M S Brown, J L Goldstein
Oct 1, 1986·Circulation·J B Meddings, J M Dietschy
Nov 1, 1986·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·L M HavekesH M Princen
Mar 1, 1986·The Journal of Clinical Investigation·B TengG R Thompson
Nov 1, 1985·Arteriosclerosis : an Official Journal of the American Heart Association, Inc·S M GrundyD W Bilheimer
Jul 1, 1982·The Journal of Clinical Investigation·Y A Kesaniemi, S M Grundy
Feb 1, 1995·Atherosclerosis·M H CummingsP H Sönksen
Apr 1, 1994·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·W R FisherP W Stacpoole
May 1, 1993·Arteriosclerosis and Thrombosis : a Journal of Vascular Biology·A D Sniderman, K Cianflone
Mar 15, 1996·The Biochemical Journal·I J Cartwright, J A Higgins
Feb 5, 2000·Atherosclerosis·A D SnidermanK Cianflone
Feb 18, 2004·Journal of Lipid Research·André J TremblayPatrick Couture
Jan 8, 2005·Arteriosclerosis, Thrombosis, and Vascular Biology·John S MillarDaniel J Rader
Nov 21, 2007·The Journal of Biological Chemistry·Yvonne LangeTheodore L Steck
Nov 1, 2008·Journal of Lipid Research·Michael S Brown, Joseph L Goldstein
Dec 17, 2008·Current Atherosclerosis Reports·Michael H Davidson
Mar 21, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Joseph L Goldstein, Michael S Brown
Jun 13, 2009·Science·Noam ZelcerPeter Tontonoz
Citations
Mar 23, 2011·Journal of Lipid Research·Eric A FisherRoger S McLeod
Feb 11, 2014·The British Journal of Nutrition·Siti N WulanGuy Plasqui
Dec 27, 2011·Steroids·Robert A Wild
Jun 2, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Max A CayoStephen A Duncan
Apr 26, 2015·Journal of Clinical Lipidology·Raul D SantosWilliam C Cromwell
Aug 30, 2017·Circulation·Jean-Philippe Drouin-ChartierPatrick Couture
May 2, 2019·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Siti N WulanGuy Plasqui
Apr 21, 2017·Clinical Science·Allan D SnidermanGerald F Watts
Mar 23, 2018·Diseases·Giovanni CiccarelliGiovanni Cimmino
Jun 18, 2017·Lipids in Health and Disease·Jean-Philippe Drouin-ChartierPatrick Couture
Jul 1, 2014·Expert Review of Endocrinology & Metabolism·Mark T Mc Auley, Kathleen M Mooney
Aug 24, 2011·Diabetes & Vascular Disease Research : Official Journal of the International Society of Diabetes and Vascular Disease·Maurizio AvernaPhilippe Brudi