Dataset Information

Sexual Dimorphism in Circadian Physiology Is Altered in LXR? Deficient Mice.

ABSTRACT: 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?) which is known to regulate glucocorticoid production in mice modulates the sex specific circadian pattern of plasma corticosterone. Lxr?(-/-) 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?(-/-) males which display a female-like phenotype. We also show that circadian expression patterns of liver 11?-hydroxysteroid dehydrogenase type 1 (11?-HSD1) and Phosphoenolpyruvate carboxykinase (Pepck) differ between sexes and are differentially altered in Lxr?(-/-) 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?(-/-) females and could be explained by the change in corticosterone profile. Together this data indicates that LXR? is a determinant of sexually dimorphic circadian patterns of key physiological parameters. The discovery of this unanticipated role for LXR? in circadian physiology underscores the importance of addressing sex differences in chronobiology studies and future LXR? targeted therapies.

SUBMITTER: Feillet C

PROVIDER: S-EPMC4777295 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Sexual Dimorphism in Circadian Physiology Is Altered in LXRα Deficient Mice.

Feillet Céline C Guérin Sophie S Lonchampt Michel M Dacquet Catherine C Gustafsson Jan-Åke JÅ Delaunay Franck F Teboul Michèle M

PloS one 20160303 3

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 (LXRα) which is kn ...[more]

PMID: 26938655

Similar Datasets

Project description:Purpose: To conduct a transcriptomic study of gene oscillations in mouse liver by RNA sequencing of total RNA samples from 6 different time points across the day. Specific interest is to see whether sex is a factor in large scale gene oscillations under ad-libitum control conditions and in response to caloric restriction diet, since caloric restriction was previously reported to affect gene oscillation Methods: Total RNA was isolated from 20 mg mouse liver tissue using mini spin column QIAGEN RNeasy Mini Kit (Ref #74104, Lot#163035346, Hilden, Germany) according to the manufacturer’s protocol. Sample purity was checked on Nano Drop 2000 (Thermo Fisher Scientific, Waltham, MA, USA) with 260/280 ratio ≥ 2.0 and 260/230 ratio ≥ 2.0 for every sample. Each sample used for the analysis had RNA integrity number > 7. The RNA sequencing was performed by Novogene Corporation Inc (Sacramento, CA, USA). After sample quality control, non-directional – polyA enrichment library was prepared using NEBNext Ultra™ II RNA Library Prep Kit for Illumina, and 50M reads (150bp, paired end) per sample were generated on Illumina NovaSeq 6000 platform. RNA-seq reads were mapped to the mouse protein coding genes (Ensembl: Mus_musculus; GRCm38) using Bowtie allowing up to 2-mismatches. The gene expected read counts and Transcripts Per Million (TPM) were estimated by RSEM (v1.2.3). The TPMs were further normalized by EBSeq R package to correct potential batch effect. Results: We have performed RNA sequencing analysis of mouse livers on Ad-libitum and timed Caloric Restriction diet across 6 time points in 24h. The results of subsequent compareRhythms analysis (R package) revealed that circadian rhythms in total RNA liver transcriptome are different between sexes of mice in both the number of oscillating genes and phase under ad-libitum diet. Caloric restriction increased the number of oscillating genes in both sexes and resulted in a larger overlap of rhythmic transcriptome between sexes, but did not eliminate the difference completely. The response of transcriptome to caloric restriction in terms of gain or loss of rhythm in gene expression profiles was also different between sexes. Additionally, we have shown that the lack of data stratification by sex might result in the failure to detect rhythmic changes in expression of some genes. Conclusions: Our study represents the first systematic analysis of the effect of sex on circadian rhythms of liver transcriptome under ad libitum and caloric restriction diets. We have shown that sex based differences exist in rhythmic transcriptome, as well as in the response of rhythmic transcriptome to diet. We are providing the data useful for both circadian and metabolic researchers and point out the gene candidates which may not be identified as rhythmic, if the data is not stratified by sex. With the help of GO analysis we have concluded that sex also influences the preference towards different processes to be regulated in rhythmic manner on transcriptional level - fatty acid metabolism and protein transport in males vs nucleic acid metabolism and RNA processing in females on ad-libitum diet. On calorie-restricted diet nucleic acid metabolism and RNA processing were enriched in males vs protein transport and signal transduction in females on calorie-restricted diet. These findings highlight a complex interaction of sex and diet in their effect on circadian rhythms in liver gene expression. All of the data from sequenced RNA samples from MALE liver were previously uploaded with the GSE211975 dataset. The current dataset only contains RNA-seq samples from FEMALE liver.

Dataset Information

Sexual Dimorphism in Circadian Physiology Is Altered in LXR? Deficient Mice.

Publications

Sexual Dimorphism in Circadian Physiology Is Altered in LXRα Deficient Mice.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets