Murdoch University Research Repository

Welcome to the Murdoch University Research Repository

The Murdoch University Research Repository is an open access digital collection of research
created by Murdoch University staff, researchers and postgraduate students.

Learn more

Hepatic iron loading in mice increases cholesterol biosynthesis

Graham, R.M., Chua, A.C.G., Carter, K.W., Delima, R.D., Johnstone, D., Herbison, C.E., Firth, M.J., O'Leary, R., Milward, E.A., Olynyk, J.K. and Trinder, D. (2010) Hepatic iron loading in mice increases cholesterol biosynthesis. Hepatology, 52 (2). pp. 462-471.

PDF - Published Version
Download (497kB)
Link to Published Version:
*Subscription may be required


ron 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 (R2 between 0.602 and 0.164), including those of the rate-limiting enzyme, 3-hydroxy-3-methylglutarate-coenzyme A reductase (Hmgcr; R2 = 0.362, P < 0.002). Hepatic cholesterol content correlated positively with hepatic iron (R2 = 0.255, P < 0.007). There was no significant relationship between plasma cholesterol and either hepatic cholesterol or iron (R2 = 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; R2 = 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.

Item Type: Journal Article
Publisher: John Wiley & Sons Inc.
Copyright: © 2010 American Association for the Study of Liver Diseases
Item Control Page Item Control Page


Downloads per month over past year