| Hepatic iron loading in mice increases cholesterol biosynthesis. | |
| | |
MedLine Citation:
|
PMID: 20683946 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Iron and cholesterol are both essential metabolites in mammalian systems, and too much or too little of either can have serious clinical consequences. In addition, both have been associated with steatosis and its progression, contributing, inter alia, to an increase in hepatic oxidative stress. The interaction between iron and cholesterol is unclear, with no consistent evidence emerging with respect to changes in plasma cholesterol on the basis of iron status. We sought to clarify the role of iron in lipid metabolism by studying the effects of iron status on hepatic cholesterol synthesis in mice with differing iron status. Transcripts of seven enzymes in the cholesterol biosynthesis pathway were significantly up-regulated with increasing hepatic iron (R(2) between 0.602 and 0.164), including those of the rate-limiting enzyme, 3-hydroxy-3-methylglutarate-coenzyme A reductase (Hmgcr; R(2) = 0.362, P < 0.002). Hepatic cholesterol content correlated positively with hepatic iron (R(2) = 0.255, P < 0.007). There was no significant relationship between plasma cholesterol and either hepatic cholesterol or iron (R(2) = 0.101 and 0.014, respectively). Hepatic iron did not correlate with a number of known regulators of cholesterol synthesis, including sterol-regulatory element binding factor 2 (Srebf2; R(2) = 0.015), suggesting that the increases seen in the cholesterol biosynthesis pathway are independent of Srebf2. Transcripts of genes involved in bile acid synthesis, transport, or regulation did not increase with increasing hepatic iron. Conclusion: This study suggests that hepatic iron loading increases liver cholesterol synthesis and provides a new and potentially important additional mechanism by which iron could contribute to the development of fatty liver disease or lipotoxicity. |
| | |
Authors:
|
Ross M Graham; Anita C G Chua; Kim W Carter; Roheeth D Delima; Daniel Johnstone; Carly E Herbison; Martin J Firth; Rebecca O'Leary; Elizabeth A Milward; John K Olynyk; Debbie Trinder |
Related Documents
:
|
11787686 - Does human lactoferrin in the milk of transgenic mice deliver iron to suckling neonates? 22494106 - The effects of high-intensity resistance exercise on the blood lipid profile and liver ... 8745736 - Effects of iron deficiency on the hepatic development of plasmodium yoelii. 18409606 - Near-field commercial aircraft contribution to nitrogen oxides by engine, aircraft type... 10980796 - Dietary nutrients and blood pressure in urban minority adolescents at risk for hyperten... 17163916 - Fat injections for facial rejuvenation: 17 years experience in 1720 patients. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
|
Title: Hepatology (Baltimore, Md.) Volume: 52 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2010 Aug |
Date Detail:
|
Created Date: 2010-08-04 Completed Date: 2010-09-07 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
|
Languages: eng Pagination: 462-71 Citation Subset: IM |
Affiliation:
|
School of Medicine and Pharmacology, University of Western Australia, Perth, WA, Australia. rmgraham@meddent.uwa.edu.au |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals Cholesterol / biosynthesis* Fatty Liver / etiology Iron / administration & dosage*, physiology* Male Mice Mice, Inbred AKR |
| Chemical | |
Reg. No./Substance:
|
57-88-5/Cholesterol; 7439-89-6/Iron |
| Comments/Corrections | |
Comment In:
|
Hepatology. 2010 Aug;52(2):408-10
[PMID:
20683940
]
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepati...
Next Document: High-dose ursodeoxycholic acid therapy for nonalcoholic steatohepatitis: a double-blind, randomized,...