title: Circadian rhythm of cholesterol synthesis in mouse liver: a statistical analysis of the post-squalene metabolites in wild-type and Crem-knock-out mice.
abstract: Circadian rhythms affect the total cholesterol levels in humans and animals, although their effect on cholesterol synthesis remain poorly understood. Here, we show for the first time that intermediates of the post-squalene portion of cholesterol synthesis also follow a circadian rhythm in the mouse liver. We used Crem-knock-out mice to investigate the effects of cAMP response element modulator (CREM) isoforms on cholesterol synthesis over time, as compared to wild-type mice. Multiple linear regression and cosinor statistical analysis were carried out on data obtained from 166 liver samples of mice, and the 24-h profiles were modelled across genotype, gender and zeitgeber time for lanosterol, 24,25-dihydrolanosterol, testis meiosis-activating sterol, and 7-dehydrocholesterol, along with cholesterol. The levels of these sterols were higher in female mice compared to males, although the genotype/gender factors showed no effects on the circadian oscillation of these sterols, except for 24,25-dihydrolanosterol. This study also highlights the importance of the statistical methods, where time, genotype and gender are the studied variables.
authors.affiliation: Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, Vrazov trg 2, Ljubljana, Slovenia.
authors.forename: Jure
authors.initials: J
authors.lastname: Ačimovič
authors.forename: Rok
authors.initials: R
authors.lastname: Košir
authors.forename: Damijana
authors.initials: D
authors.lastname: Kastelec
authors.forename: Martina
authors.initials: M
authors.lastname: Perše
authors.forename: Gregor
authors.initials: G
authors.lastname: Majdič
authors.forename: Damjana
authors.initials: D
authors.lastname: Rozman
authors.forename: Katarina
authors.initials: K
authors.lastname: Košmelj
authors.forename: Marko
authors.initials: M
authors.lastname: Goličnik
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000096:biosynthesis*; D002940:Circadian Rhythm; D051786:Cyclic AMP Response Element Modulator / Q000235:genetics; D003627:Data Interpretation, Statistical; D005260:Female; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013185:Squalene / Q000378:metabolism*
chemical_list: C497411:Crem protein, mouse; D051786:Cyclic AMP Response Element Modulator; D013185:Squalene; D002784:Cholesterol