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Cholesterol precursors: more than mere markers of biosynthesis

Brown, Andrew J.a; Ikonen, Elinab,c; Olkkonen, Vesa M.c

Current Opinion in Lipidology: April 2014 - Volume 25 - Issue 2 - p 133–139
doi: 10.1097/MOL.0000000000000038
GENETICS AND MOLECULAR BIOLOGY: Edited by Robert A. Hegele

Purpose of review: Circulating levels of cholesterol precursors in the body have proven their value over the years as indicators of in-vivo cholesterol synthesis. However, there is growing interest in their potential as markers of various disease states. The purpose of this review is to evaluate current literature on cholesterol precursors as disease markers.

Recent findings: Firstly, we focus on studies linking circulating squalene with the risk of cardiovascular disease. Secondly, we explore the interplay between cholesterol precursors (7-dehydrocholesterol and desmosterol) and the enzymes that act upon them (DHCR7 and DHCR24) in the context of liver disease. For instance, recent findings indicate that circulating desmosterol is elevated in nonalcoholic steatohepatitis. This may be linked to this regulatory cholesterol precursor being produced in and effluxed from hepatocytes, or alternatively from lipid-laden hepatic macrophages (Kupffer cells), which play an important role in the cause of nonalcoholic steatohepatitis. Desmosterol is also implicated in Hepatitis C virus replication, and hence may also be involved in viral fatty liver disease, possibly contributing to virus pathogenicity and/or host defense. Furthermore, there is increasing evidence that the activity of DHCR7 may affect chronic liver diseases by influencing vitamin D levels.

Summary: Beyond their accepted application as markers of cholesterol synthesis, cholesterol precursors have potential both as disease indicators, and for providing deeper insights into the disease process.

aSchool of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales, Australia

bInstitute of Biomedicine, Anatomy, University of Helsinki

cMinerva Foundation Institute for Medical Research, Helsinki, Finland

Correspondence to Prof. Andrew J. Brown, School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, NSW 2052, Australia. Tel: +61 2 9385 2005; fax: +61 2 9385 1483; e-mail: aj.brown@unsw.edu.au

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