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Steroid Hormones Control Circadian Elovl3 Expression in Mouse Liver

The Wenner-Gren Institute (A.B., A.Jac., A.Jak.), The Arrhenius Laboratories F3, Stockholm University, SE-106 91 Stockholm, Sweden; Centre de Genètica Mèdica i Molecular (S.F., A.P.), Institut d'Investigació Biomèdica de Bellvitge; Institut de Neuropatologia de Bellvitge (S.F., A.P.), and Institut d'Investigació Biomèdica de Bellvitge and Universitat de Barcelona, Barcelona 08028, Spain; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain; and Catalan Institution of Research and Advanced Studies, ICREA (A.P.), 08010 Barcelona, Spain

Address all correspondence and requests for reprints to: Anders Jacobsson, The Wenner-Gren Institute, The Arrhenius Laboratories F3, Stockholm University, SE-10691 Stockholm, Sweden. 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. 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 on 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 Zeitgeber time (ZT) 20, 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 9 d 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 ATP-binding cassette, subfamily D(ALD), member 2 ablated mice and suppressed in ATP-binding cassette subfamily D(ALD) member 2 overexpressing mice, implying a tight cross talk between very long chain fatty acid synthesis and peroxisomal fatty acid oxidation.

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