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This version published online on February 21, 2008
Endocrinology, doi:10.1210/en.2007-1402
A more recent version of this article appeared on June 1, 2008
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Submitted on October 12, 2007
Accepted on February 14, 2008

Steroid hormones control circadian Elovl3 expression in mouse liver

Annelie Brolinson, Stéphane Fourcade, Andreas Jakobsson, Aurora Pujol, and Anders Jacobsson*

The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden; Centre de Genètica Mèdica i Molecular, Institut d'Investigació Biomèdica de Bellvitge (IDIBELL); Institut de Neuropatologia de Bellvitge, IDIBELL and Universitat de Barcelona, Spain; CIBER on Rare Diseases (CIBERER), Barcelona, Spain; Catalan Institution of Research and Advanced Studies (ICREA) 08010 Barcelona, Spain

* To whom correspondence should be addressed. E-mail: anders.jacobsson{at}wgi.su.se.

The Elovl3 gene belongs to the Elovl gene family, which encodes for enzymes involved in the elongation of very long chain fatty acids (VLCFA). The recognized role for the enzyme is to control the elongation of saturated and monounsaturated fatty acids up to 24 carbons in length. Elovl3 was originally identified as a highly expressed gene in brown adipose tissue upon cold exposure. Here we show that hepatic Elovl3 mRNA expression follows a distinct diurnal rhythm exclusively in mature male mice, with a sharp increase early in the morning ZT20, peaks around ZT2 and is back to basal level at the end of the light period at ZT10. In female mice and sexually immature male mice the Elovl3 expression was constantly low. Fasting and refeeding mice with chow or high fat diet did not alter the Elovl3 mRNA levels. However, animals that were exclusively fed during the day for nine days displayed an inverted expression profile. In addition, we show that Elovl3 expression is transcriptionally controlled and significantly induced by the exposure of the synthetic glucocorticoid dexamethasone. Taken together, these data suggest that Elovl3 expression in mouse liver is under strict diurnal control by circulating steroid hormones such as glucocorticoids and androgens. Finally, Elovl3 expression was found to be elevated in peroxisomal transporter ABCD2 ablated mice and suppressed in ABCD2 overexpressing mice, implying a tight cross- talk between VLCFA synthesis and peroxisomal fatty acid oxidation.


Key words: elongase • fatty acids • circadian • gender







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