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LXR activation induces insulin resistance in primary human adipocytes

ABSTRACT: The effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling.

ORGANISM(S): synthetic construct Homo sapiens

PROVIDER: GSE41223 | GEO | 2012/09/29

SECONDARY ACCESSION(S): PRJNA176226

REPOSITORIES: GEO

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LXR activation induces insulin resistance in primary human adipocytes

Project description:The effects of LXR stimulation by GW3965 treatment on global mRNA and miRNA expression in primary human in vitro differentiated adipocytes was investigated using microarray profiling. Preadipocytes were isolated from human adipose tissue obtained from healthy subjects and differentiated in vitro. Around day 11 of differentiation cells were treated with the Liver X Receptor agonist GW3865 for 24 h and lysed. Total RNA as prepared and hybridised biotinylated complementary RNA to Gene 1.0 ST Arrays using standardized protocols (Affymetrix Inc., Santa Clara, CA). The GeneChip Operating Software Version 1.4 was used for analysis. Arrays were normalized using PLIER and all samples were subjected to an all-probeset scaling-to-target signal of 100. Preadipocytes were isolated from human adipose tissue obtained from healthy subjects and differentiated in vitro. Around day 11 of differentiation cells were treated with the Liver X Receptor agonist GW3865 for 12 h and lysed. Total RNA was prepared and and labelled using the FlashTag biotin HSR labeling kit (Genisphere Inc., Hatfield, PA) according to the supplier's protocol. The labelled samples were placed in a hybridization cocktail mix containing 4% formamide and hybridised overnight to Affymetrix miRNA Arrays (Affymetrix Inc.) following the indicated Genisphere protocol. The arrays were washed, stained and scanned in an Affymetrix GCS 3000 scanner. Signal intensities and present calls were generated by using the microRNA QC tool by Affymetrix using default settings i.e. Background Adjustment: BC-CG adjust, Normalization: Quantile: Summarization: Median Polish.

2012-09-29 | E-GEOD-41223 | biostudies-arrayexpress

Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA

Project description:Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA shows differential effect of Ulk1 KD on LXr responsive genes AML-12 cells co-treated with 0.75mM PA+/- 10ÂµM GW3965 for 24 h +/- Ulk1 SiRNA

2016-03-31 | E-GEOD-74059 | biostudies-arrayexpress

Bulk RNA-seq of intestinal organoids upon treatment with LXR agonist GW3965

Project description:Liver X Receptor (LXR) activation in intestinal epithelial organoids promotes their growth in vitro. To investigate the downstream effect of LXR activation in intestinal epithelial cells and identify potential pathways driving regeneration, we carried out an unbiased transcriptomic analysis of intestinal epithelial organoids stimulated with the LXR agonist GW3965. In detail, wild type small intestinal crypts were seeded in vitro and stimulated with vehicle (DMSO) or GW3965. After six hours, closing crypts (organoids) were collected for RNA extraction and were analyzed by RNA sequencing.

2023-06-11 | GSE152283 | GEO

Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA

Project description:Transcriptional regulation of genes in AML12 cells treated with Palmitic acid, LXR lingand (GW3965) and Ulk1 siRNA shows differential effect of Ulk1 KD on LXr responsive genes

2016-03-31 | GSE74059 | GEO

Differential translatome in the sensory neurons of the DRG treated with LXR agonist

Project description:We show differences in translatome of the sensory neurons of the DRG primary neurons treated with LXR agonist GW3965.

2022-06-29 | GSE198898 | GEO

RNA-seq of primary human CD4+ T cells treated with the LXR agonist GW3965, with and without TCR stimulation

Project description:We used RNA-sequencing to determine the transcriptional response to liver X receptor (LXR) activation in primary human CD4+ T cells, both at rest and under activation conditions. CD4+ T cells were isolated from 3 healthy donors and treated with the synthetic LXR agonist GW3965 (GW) for 24 hours. Gene expression was compared to control samples (CTRL) treated with the LXR antagonist GSK1440233. To activate the T cell antigen receptor (TCR), cells were pre-treated with CTRL/GW alone for 6 hours then transferred to plates containing anti-CD3 and anti-CD28 for a further 18 hours.

2021-04-30 | E-MTAB-9141 | biostudies-arrayexpress

Intestine-specific activation of LXR via low-dose oral administration of GW3965

Project description:Generation of high density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most HDL in blood, small intestines also can synthesize HDL. However, distinct functions for intestinal HDL are unknown. Here we designed intestine-specific activation of LXR via low-dose administration of GW3965, LXR agonist. The liver status was improved by therapeutics that elevated and depended upon intestinal HDL production via GW3965. Thus, protection of the liver from injury in response to gut-derived signals like LPS is a major function of intestinally synthesized HDL.

2021-10-06 | GSE167983 | GEO

LXR-dependent gene expression in mouse bone marrow derived macrophages

Project description:Bone marrow derived macrophages were isolated from C57BL/6J (LXR positive) and LXRalpha +LXRbeta double knockout mice (DKO) that had been treated with vehicle, Kado2-lipid A (KLA, and inflammatory stimulus), acetylated LDL (AcLDL, a mimic of pro-atherogenic lipoprotein particles) and GW3965 (GW, a synthetic LXR agonist) for 17 hours. Following treatment RNA was isolated and RNA-Seq was performed.

2018-08-17 | GSE118656 | GEO

LXR activation in RAW264.7 mouse macrophages expressing LXRalpha.

Project description:To identify novel LXR target genes, we conducted transcriptional profiling studies using RAW264.7 cells ectopically expressing LXRalpha Total RNA was isolated from RAW264.7 macrophages ectopically expressing LXRalpha as described in Venkateswaran et al. (2000); PNAS 97, 12097-12102. Cells were cultured with DMSO or GW3965 (1 μM) and LG268 (100 nM). Transcriptional profiling was performed at the UCLA microarray core facility using murine Affymetrix 430 2.0 microarrays.

2009-08-01 | E-GEOD-17088 | biostudies-arrayexpress

Transcriptional effects of LXR nuclear receptors on M-CSF-derived macrophages

Project description:Analysis of the role of LXR transcriptions factors on the transcriptional signature of human M-CSF-dependent monocyte-derived macrophages. Methods: Human Peripheral Blood Mononuclear Cells (PBMC) were isolated from buffy coats from donors over a Lymphoprep gradient according to standard procedures. Monocytes were purified from PBMC by magnetic cell sorting using anti-CD14 microbeads (>95% CD14+ cells). Monocytes from three independent donors (0.5 x 106 cells/ml, >95% CD14+ cells) were treated with LXR agonist GW3965 (1 uM, Tocris), LXR antagonist GSK2033 (1 uM, Tocris), GW3965 and GSK2033, or dimethyl sulfoxide (DMSO) as vehicle. In the dual condition, the antagonist was added 1-hour prior to agonist treatment. Then, monocytes were cultured in RPMI 1640 supplemented with 10% fetal bovine serum (FBS) at 37°C in a humidified atmosphere with 5% CO2 and 21% O2 for 7 days in the presence of 1000 U/ml M-CSF, with cytokine addition every two days.

2022-03-24 | GSE156783 | GEO

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