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Transcriptomic effect of high-fat diet and PCN treatment on the livers of of PXR deficient mice

ABSTRACT: PXR deficient mice were fed high-fat diet (HFD) and treated with PCN, a selective murine PXR agonist, and hepatic effects of the high-fat diet feeding and PCN treatment were studied.

ORGANISM(S): Mus musculus

PROVIDER: GSE162196 | GEO | 2023/09/22

REPOSITORIES: GEO

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	GSE162196_HFD_PCN_vs_HFD_Vehicle.txt.gz	Txt
	GSE162196_HFD_vs_Chow.txt.gz	Txt

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Transcriptomic effect of high-fat diet and PCN treatment on the duodenum of C57BL/6N mice.

Project description:C57BL/7N mice were fed high-fat diet (HFD) and treated with Pregnenolone-16alfa-carbonitrile (PCN), a selective murine PXR agonist, and duodenal effects of the high-fat diet feeding and PCN treatment were studied.

2023-09-22 | GSE163407 | GEO

Transcriptomic effect of high-fat diet and PCN treatment on the skeletal muscle of C57BL/6N mice.

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Transcriptomic effect of high-fat diet and PCN treatment on the gonadal white adipose tissue of C57BL/6N mice.

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Atorvastatin regulates hepatic transcriptome PXR dependently but distinct from pregnenolone 16α-carbonitrile and does not induce PXR-mediated liver steatosis

Project description:Several drugs induce liver steatosis through pregnane X receptor (PXR)-mediated mechanism. Atorvastatin is a PXR ligand but is still safe even in patients with metabolic dysfunction-associated steatotic liver disease. To reveal differences between atorvastatin and other PXR ligands, we characterized the effect of atorvastatin on PXR-mediated gene regulation and liver steatosis in mice. Mice were treated orally with atorvastatin, a classical PXR ligand pregnenolone 16α-carbonitrile (PCN), or pravastatin, a statin not activating PXR. Atorvastatin treatment was also performed in PXR knockout mice. Analysis of liver transcriptomics after four-day treatment indicated that atorvastatin regulates genes almost exclusively through PXR. Atorvastatin and PCN regulated partially overlapping, but distinct set of genes and Cyp3a11 was not induced by atorvastatin. Pathway analysis indicated that the atorvastatin treatment predominantly induced genes involved in cholesterol synthesis, while PCN affected pathways involved in growth, proliferation, and steatosis. PCN increased nuclear SREBP1 protein level while atorvastatin increased both SREBP1 and SREBP2. In high-fat diet (HFD)-fed mice, 28-day oral treatment with PCN aggravated diet-induced liver steatosis while atorvastatin had no effect. 28-day atorvastatin treatment reduced the hepatic expression of PXR, and its effect on cholesterol synthesis genes disappeared. PCN did not influence PXR expression, and the Cyp3a11 expression remained induced still after 28 days. Among the lipogenic genes studied, Scd1 was the only one significantly induced by PCN after 28-day treatment in the HFD-fed mice. In summary, atorvastatin regulates mouse liver transcriptomics PXR dependently but differently from PCN and represses PXR in long-term treatment in the HFD-fed mice. Unlike PCN, atorvastatin does not promote liver steatosis.

2026-05-19 | GSE297644 | GEO

Atorvastatin regulates hepatic transcriptome PXR dependently but distinct from pregnenolone 16α-carbonitrile and does not induce PXR-mediated liver steatosis [ATAC-seq]

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Transcriptomic effect of high-fat diet and PCN treatment on the livers of of PXR deficient mice

Project description:Transcriptomic effect of high-fat diet and PCN treatment on the livers of of PXR deficient mice

| PRJNA680921 | ENA

Effect of PCN on CAR and PXR regulated genes involved in circadian rhythm, drug metabolism and cholesterol homeostasis

Project description:The nuclear receptor PXR (Pregnane X rreceptor) mediates the effects of pregnenolone-16alpha-carbonitrile (PCN) on gene transcription. The relative role of PXR and also CAR to the induction response by PCN was studied on cDNA arrays containing 320 (Steroltalk V2) genes (genes involved in cyrcadian rhythm, drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PCN for gene expression within the European Framework V program âSteroltalkâ (www.steroltalk.net). Results from these experiments show the complex role of PXR receptor in the expression of genes involved in cyrcadian rhythm, drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 40mg/kg PCN or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the PCN treated ones and hybridized to Steroltalk V2 arrays.

2010-05-16 | E-GEOD-12537 | biostudies-arrayexpress

Effect of PCN on CAR and PXR regulated genes involved in circadian rhythm, drug metabolism and cholesterol homeostasis

Project description:The nuclear receptor PXR (Pregnane X rreceptor) mediates the effects of pregnenolone-16alpha-carbonitrile (PCN) on gene transcription. The relative role of PXR and also CAR to the induction response by PCN was studied on cDNA arrays containing 320 (Steroltalk V2) genes (genes involved in cyrcadian rhythm, drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PCN for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments show the complex role of PXR receptor in the expression of genes involved in cyrcadian rhythm, drug metabolism and cholesterol biosynthesis.

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Project description:Many environmentally-relevant chemicals and drugs activate the nuclear receptor pregnane X receptor (PXR). Activation of PXR can lead to increases in liver weight in part through hepatocyte replication similar to a large number of compounds that activate other nuclear receptors such as the peroxisome proliferator-activated receptor alpha and the constitutive activated receptor (CAR). PXR controls the expression of a large battery of genes involved in xenobiotic metabolism. Identification of genes that are accurate predictors of PXR activation would be useful in high-throughput screens to assess potential toxicity and drug-drug interactions. Here, we identified PXR-dependent genes in the mouse liver after exposure to pregnenolone 16alpha-carbinonitrile (PCN), a chemical that is often used as a model PXR agonist.

2014-09-30 | GSE55746 | GEO

Transcriptomic effect of high-fat diet and PCN treatment on mouse liver

Project description:PCN, a selective murine PXR agonist, was administered to obese mice with the goal to investigate what transcriptional changes PXR activation cause in the livers of obese mice.

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