The ABC of hepatic and intestinal cholesterol transport
- PMID: 16596811
- DOI: 10.1007/3-540-27661-0_17
The ABC of hepatic and intestinal cholesterol transport
Abstract
The liver and (small) intestine are key organs in maintenance of cholesterol homeostasis: both organs show active de novo cholesterogenesis and are able to transport impressive amounts of newly synthesized and diet-derived cholesterol via a number of distinct pathways. Cholesterol trafficking involves the concerted action of a number of transporter proteins, some of which have been identified only recently. In particular, several ATP-binding cassette (ABC) transporters fulfil critical roles. For instance, the ABCG5/ABCG8 couple is crucial for hepatobiliary and intestinal cholesterol excretion, while ABCA1 is essential for high-density lipoprotein formation and, hence, for inter-organ trafficking of the highly water-insoluble cholesterol molecules. Very recently, the Niemann-Pick C1-like 1 protein has been identified as a key player in cholesterol absorption by the small intestine and may represent a target of the cholesterol absorption inhibitor ezetimibe. Alterations in hepatic and intestinal cholesterol transport affect circulating levels of atherogenic lipoproteins and thus the risk for cardiovascular disease. This review specifically deals with the processes of hepatobiliary cholesterol excretion and intestinal cholesterol absorption as well as the interactions between these important transport routes. During the last few years, insight into the mechanisms of hepatic and intestinal cholesterol transport has greatly increased not in the least by the identification of involved transporter proteins and the (partial) elucidation of their mode of action. In addition, information has become available on (transcription) factors regulating expression of the encoding genes. This knowledge is of great importance for the development of a tailored design of novel plasma cholesterol-lowering strategies.
Similar articles
-
Hepatic ABCG5 and ABCG8 overexpression increases hepatobiliary sterol transport but does not alter aortic atherosclerosis in transgenic mice.J Biol Chem. 2004 May 28;279(22):22913-25. doi: 10.1074/jbc.M402838200. Epub 2004 Mar 25. J Biol Chem. 2004. PMID: 15044450
-
Abcc6 deficiency in mice leads to altered ABC transporter gene expression in metabolic active tissues.Lipids Health Dis. 2019 Jan 5;18(1):2. doi: 10.1186/s12944-018-0943-x. Lipids Health Dis. 2019. PMID: 30611276 Free PMC article.
-
Pravastatin Modulate Niemann-Pick C1-Like 1 and ATP-Binding Cassette G5 and G8 to Influence Intestinal Cholesterol Absorption.J Pharm Pharm Sci. 2015;18(5):765-72. doi: 10.18433/j3m029. J Pharm Pharm Sci. 2015. PMID: 26670369
-
Sterol transporters: targets of natural sterols and new lipid lowering drugs.Pharmacol Ther. 2005 Mar;105(3):333-41. doi: 10.1016/j.pharmthera.2004.10.011. Epub 2004 Dec 9. Pharmacol Ther. 2005. PMID: 15737409 Review.
-
ABCG5/ABCG8 in cholesterol excretion and atherosclerosis.Clin Chim Acta. 2014 Jan 20;428:82-8. doi: 10.1016/j.cca.2013.11.010. Epub 2013 Nov 16. Clin Chim Acta. 2014. PMID: 24252657 Review.
Cited by
-
The regulation of Niemann-Pick C1-Like 1 (NPC1L1) gene expression in opposite direction by Bacteroides spp. and related outer membrane vesicles in Caco-2 cell line.J Diabetes Metab Disord. 2020 Apr 22;19(1):415-422. doi: 10.1007/s40200-020-00522-3. eCollection 2020 Jun. J Diabetes Metab Disord. 2020. PMID: 32550192 Free PMC article.
-
Management of Hypercholesterolemia Through Dietary ß-glucans-Insights From a Zebrafish Model.Front Nutr. 2022 Jan 12;8:797452. doi: 10.3389/fnut.2021.797452. eCollection 2021. Front Nutr. 2022. PMID: 35096942 Free PMC article.
-
Effect of dietary fat on hepatic liver X receptor expression in P-glycoprotein deficient mice: implications for cholesterol metabolism.Lipids Health Dis. 2008 Jun 11;7:21. doi: 10.1186/1476-511X-7-21. Lipids Health Dis. 2008. PMID: 18547429 Free PMC article.
-
MicroRNA Regulation of Cholesterol Metabolism.Cholesterol. 2012;2012:847849. doi: 10.1155/2012/847849. Epub 2012 Aug 5. Cholesterol. 2012. PMID: 22919472 Free PMC article.
-
Looking into the future of foods and health.Innovation (North Syd). 2008 Jul;10(1):109-120. doi: 10.5172/impp.453.10.1.109. Innovation (North Syd). 2008. PMID: 23950694 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical