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Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Role of Per2 in the control of liver glycogen metabolism

ABSTRACT: To investigate the role of Per2 in glucose metabolism in-vivo we used mice bearing a targeted gene mutation in the Per2 gene (Per2brdm) and thus unable to express a functional Per2 protein. Mice were hosted in our standard mouse facility in a 12-hour light and 12-hour dark cycle. Wt and Per2brdm mice were fed with either standard chow diet or high-fat diet for 24 weeks and analyzed for glucose homeostasis. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed on mice food deprived for 7 hours. For pyruvate tolerance test (PTT) mice were fasted for 14 hours. Glucose levels were measured over 12 hours starvation time-courses during the light and the dark phase. Fed and fasting blood glucose and hepatic glycogen content were measured over different circadian time-points. To investigate the role of Per2 in the control of liver gene expression we performed DNA-microarray analysis of RNA preparations from liver of Per2brdm and WT mice. We extracted total RNA from liver of four different Per2brdm and WT mice. Mice from the same cohort were sacrificed after 8 hours of starvation. After normalization we performed a fold change comparison selecting probes with a p value < 0.05.

ORGANISM(S): Mus musculus

SUBMITTER: Alessandro Provenzani

PROVIDER: E-GEOD-30139 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Role of Per2 in the control of liver glycogen metabolism

Project description:To investigate the role of Per2 in glucose metabolism in-vivo we used mice bearing a targeted gene mutation in the Per2 gene (Per2brdm) and thus unable to express a functional Per2 protein. Mice were hosted in our standard mouse facility in a 12-hour light and 12-hour dark cycle. Wt and Per2brdm mice were fed with either standard chow diet or high-fat diet for 24 weeks and analyzed for glucose homeostasis. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed on mice food deprived for 7 hours. For pyruvate tolerance test (PTT) mice were fasted for 14 hours. Glucose levels were measured over 12 hours starvation time-courses during the light and the dark phase. Fed and fasting blood glucose and hepatic glycogen content were measured over different circadian time-points. To investigate the role of Per2 in the control of liver gene expression we performed DNA-microarray analysis of RNA preparations from liver of Per2brdm and WT mice.

2013-09-02 | GSE30139 | GEO

Proteomic analysis of fatty liver induced by starvation of medaka fish larvae

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Single six hours sleep deprivation causes glucose intolerance and hepatic steatosis.

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Circadian proteome atlas of wild-type and Per1-/-/Per2-/- mice models across eight organs

Project description:a circadian proteome atlas of eight organs, namely suprachiasmatic nucleus (SCN), hypothalamus (HPOA), liver (LIV), gall bladder (GBD), brown adipose tissue (BAT), kidney (KDN), heart (HEA) and muscle (MUS), from wild-type (WT) and Per1-/-/Per2-/- (DKO) mice housed under constant darkness and ad libitum feeding, collected every two hours for deep proteomic analysis over two days

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Expression data from white and brown adipose tissue (WAT and BAT) of per2-/- and control mice

Project description:We found that the circadian protein PER2 interacts with the nuclear receptor PPARgamma to repress its activity. PPARgamma is a master regulator of adipogenesis and lipid metabolism and is very abundant in adipose tissue. We used microarrays to detail the global program of gene expression in adipose tissue lacking the per2 gene. This analysis identified several PPARgamma target genes up-regulated in adipose tissue from per2-/- mice. Per2-/- and per2+/+ male mice (Bae et al., 2001) were housed under 12 hr light/12 hr dark (LD) cycles. Mice 20 weeks old were sacrificed at the same time and adipose tissue (WAT and BAT) was collected for RNA extraction. 3 biological replicates per mouse/tissue.

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Daylight regulation of cardiac gene expression in wild type and Per2 deficient mice.

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Transcription profiling of mouse liver response to a glucose challenge in healthy and insulin resistant C57BL/6J mice

Project description:The goal of this experiment is to compare the transcriptional response to a metabolic stressor (glucose bolus) between healthy and insulin resistant mouse liver. Mice with an isogenic background (C57BL/6J mice) were fed diets for 12 weeks containing either 10 or 45% fat by energy (mainly palm oil) after 2 weeks of adaptation to laboratory conditions with a control diet. The animals were subjected to a glucose tolerance test at the end of the feeding trial and liver samples were taken 0 min, 40 min, 2, 18 and 48 h after the glucose challenge. Glucose was injected via the i.p. route at 1 p.m. in all groups and animals had free access to feed during the challenge (no fasting). For more details, see Baccini et al (pmid=19034556)

2012-03-21 | E-MTAB-601 | biostudies-arrayexpress

Transcriptome Sequencing Analysis (RNA-Seq) of Bone Marrow Hematopoietic Stem Cells from Per2-mutant Mice

Project description:Circadian rhythm (CR) and environmental low-dose radiation (LDR) evident on Earth’s surface may have coordinated in the evolution of early life; disturbed CR and/or overexposure to radiation are linked with aging and many human diseases including cancer. Although CR affects tumor response and normal tissue radiosensitivity in cancer radiotherapy, it is unclear how CR proteins function in LDR induced radioprotection. Herein, we demonstrated that mice carrying a deficient Period2 gene (C57BL-Per2 def ), a core CR regulator, were highly sensitive to radiation. Compared to Per2 wt mice, the population of bone marrow hemopoietic stem cells (BMHSCs) was reduced and a cluster of genes responsible for DNA damage repair and mitochondrial metabolism was silenced in the Per2 def BMHSCs . Consistently, unlike Per2 wt human and mouse cells capable of inducible radioresistance by LDR, Per2 def cells failed to induce such adaptive protection. Furthermore, LDR enhanced PER2 protein level together with phosphorylated GSK3β (pGSK3β) in the Wnt/β-catenin signaling pathway. Interaction of PER2 with pGSK3β activated β -catenin that in turn transactivated Per2 and other prosurvival genes. These results provide new insights into how CR and LDR communicate in genotoxic stress response. The PER2/pGSK3β/β-catenin/Per2 pathway may serve as a therapeutic approach to reduce normal cell injury in cancer radiotherapy.

2022-11-04 | GSE184407 | GEO

Differential Gene Regulation during murine in vivo heart ischemia comparing wildtype and Per2 deficient mice

Project description:Disruption of peripheral circadian rhyme pathways dominantly leads to metabolic disorders. Studies on circadian rhythm proteins in the heart indicated a role for Clock or Per2 in cardiac metabolism. In fact, Per2-/- mice have larger infarct sizes with a deficient lactate production during myocardial ischemia. To test the hypothesis that cardiac Per2 represents an important regulator of cardiac metabolism during myocardial ischemia, we performed lactate measurements during reperfusion in Per1-/-, Per2-/- or wildtype mice followed by gene array studies using various ischemia-reperfusion protocols comparing wildtype and Per2-/- mice. Lactate measurements in whole blood confirmed a dominant role of Per2 for lactate production during myocardial ischemia. Surprisingly, high-throughput gene array analysis of eight different conditions on one 24-microarray plate revealed dominantly lipid metabolism as differentially regulated pathway in wildtype mice when compared to Per2-/-. In all treatment groups, the enzyme enoyl-CoA hydratase, which is essential in fatty acid beta-oxidation, was regulated in wildtype animals only. Studies using nuclear magnet resonance imaging (NMRI) confirmed altered fatty acid populations with higher mono-unsaturated fatty acid levels in hearts from Per2-/- mice. Unexpectedly, studies on gene regulation during reperfusion revealed solely pro inflammatory genes as differentially regulated 'Per2-genes'. Subsequent studies on inflammatory markers showed increasing IL6 or TNFa levels during reperfusion in Per2-/- mice. In summary, these studies reveal a novel role of cardiac Per2 for fatty acid metabolism or inflammation during myocardial ischemia and reperfusion.

2013-08-21 | GSE45818 | GEO

RNA-Seq Analysis of Wild Type and Scn5aΔ/+ left ventricle at dark:light and light:dark phase transitions

Project description:We investigated differences in gene expression in left ventricular tissue from WT and ΔKPQ (Scn5aΔ/+) mice. Tissue was collected diurnally at the phase transitions from dark to light (D:L) and light to dark (L:D). We employed RNAseq (Novogene) to examine potential variances between the two strains of mice, as well as, any differences in expression at the two time points. RNAseq provided a snapshot of gene expression which revealed an intact molecular clock for both strains. Previous studies have demonstrated circadian peak or trough at the light phase changes in cardiac tissue in mice for many core molecular clock components. Similar to these studies both strains demonstrated a significant difference in expression between core molecular clock genes Bmal1, Clock, Per1, Per2, Per3 assessed at the phase transitions. This assessment revealed 39 diurnally expressed genes. To our surprise, only 6 genes were differently expressed between the two strains of mice.

2020-03-06 | GSE146405 | GEO

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