Sexual Dimorphism in Circadian Physiology Is Altered in LXR[alpha] Deficient Mice

The mammalian circadian timing system coordinates key molecular, cellular and physiological processes along the 24-h cycle. Accumulating evidence suggests that many clock-controlled processes display a sexual dimorphism. In mammals this is well exemplified by the difference between the male and fema...

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Veröffentlicht in:PloS one 2016-03, Vol.11 (3), p.e0150665
Hauptverfasser: Feillet, Céline, Guérin, Sophie, Lonchampt, Michel, Dacquet, Catherine, Gustafsson, Jan-Åke, Delaunay, Franck, Teboul, Michèle
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Guérin, Sophie
Lonchampt, Michel
Dacquet, Catherine
Gustafsson, Jan-Åke
Delaunay, Franck
Teboul, Michèle
description The mammalian circadian timing system coordinates key molecular, cellular and physiological processes along the 24-h cycle. Accumulating evidence suggests that many clock-controlled processes display a sexual dimorphism. In mammals this is well exemplified by the difference between the male and female circadian patterns of glucocorticoid hormone secretion and clock gene expression. Here we show that the non-circadian nuclear receptor and metabolic sensor Liver X Receptor alpha (LXR[alpha]) which is known to regulate glucocorticoid production in mice modulates the sex specific circadian pattern of plasma corticosterone. Lxr[alpha].sup.-/- males display a blunted corticosterone profile while females show higher amplitude as compared to wild type animals. Wild type males are significantly slower than females to resynchronize their locomotor activity rhythm after an 8 h phase advance but this difference is abrogated in Lxr[alpha].sup.-/- males which display a female-like phenotype. We also show that circadian expression patterns of liver 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1) and Phosphoenolpyruvate carboxykinase (Pepck) differ between sexes and are differentially altered in Lxr[alpha].sup.-/- animals. These changes are associated with a damped profile of plasma glucose oscillation in males but not in females. Sex specific alteration of the insulin and leptin circadian profiles were observed in Lx[alpha].sup.-/- females and could be explained by the change in corticosterone profile. Together this data indicates that LXR[alpha] is a determinant of sexually dimorphic circadian patterns of key physiological parameters. The discovery of this unanticipated role for LXR[alpha] in circadian physiology underscores the importance of addressing sex differences in chronobiology studies and future LXR[alpha] targeted therapies.
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We also show that circadian expression patterns of liver 11[beta]-hydroxysteroid dehydrogenase type 1 (11[beta]-HSD1) and Phosphoenolpyruvate carboxykinase (Pepck) differ between sexes and are differentially altered in Lxr[alpha].sup.-/- animals. These changes are associated with a damped profile of plasma glucose oscillation in males but not in females. Sex specific alteration of the insulin and leptin circadian profiles were observed in Lx[alpha].sup.-/- females and could be explained by the change in corticosterone profile. Together this data indicates that LXR[alpha] is a determinant of sexually dimorphic circadian patterns of key physiological parameters. 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subjects Comparative analysis
Corticosterone
Gene expression
Genes
Leptin
Liver
Physiological aspects
title Sexual Dimorphism in Circadian Physiology Is Altered in LXR[alpha] Deficient Mice
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