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Diet-dependent cardiovascular lipid metabolism controlled by hepatic LXRα

ABSTRACT: Microarray analysis of liver RNA from male Low Density Lipoprotein Receptor null mice on C57B6 background expressing human LXR alpha or GFP (control) via adeno-associated virus (AAV2.8) gene transfer, under control of the liver specific human thyroxine binding globulin promoter. Samples are from 8 month old mice, with AAV treatment at age of 10 weeks, on Western diet for 12 weeks prior experiment. The synthetic LXR ligand T0901317 (5mg/kg) or vehicle was administered for 3 days by i.p. injection to designated mice. Keywords = LXR alpha Keywords = SREBP1 Keywords = diet Keywords = lipid metabolism Keywords = atherosclerosis Keywords: repeat sample

ORGANISM(S): Mus musculus

PROVIDER: GSE2644 | GEO | 2005/05/12

SECONDARY ACCESSION(S): PRJNA92291

REPOSITORIES: GEO

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Transcription profiling of livers from Low Density Lipoprotein Receptor null mice expressing human LXR alpha to explore the molecular basis of metabolic effects of increased hepatic hLXR alpha.

Project description:Microarray analysis of liver RNA from male Low Density Lipoprotein Receptor null mice on C57B6 background expressing human LXR alpha or GFP (control) via adeno-associated virus (AAV2.8) gene transfer, under control of the liver specific human thyroxine binding globulin promoter. Samples are from 8 month old mice, with AAV treatment at age of 10 weeks, on Western diet for 12 weeks prior experiment. The synthetic LXR ligand T0901317 (5mg/kg) or vehicle was administered for 3 days by i.p. injection to designated mice.

2007-08-31 | E-GEOD-2644 | biostudies-arrayexpress

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2013-09-05 | GSE39079 | GEO

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Project description:To investigate the mechanism of hepatic Activin A in atherosclerosis, we studied LDLR-/- mice on a Western diet for 12 weeks and used adeno-associated viral vectors with a liver-specific thyroxine binding globulin (TBG) promoter to express Activin A or GFP (control) We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different livers in each group

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Project description:The aim of this study was to investigate the effect of T0901317 LXR agonist on Retinoic Acid Receptor (RAR) family gene expression. T0901317 alone increase RARalpha gene expression in monocytes and the effects of the co treatment of the cells with T0901317 and a specific RARalpha agonist (AM580) were further studied. For this monocytes were treated for 24h with DMSO or T0901317 to induce RARalpha expression and in a second step cells were treated or not with AM580 for another 24h period. Gene expression was analysed for all the treatments (T0901317, AM580 or T0901317+AM580) and we focussed on genes which expression was synergitically induced by the co treatment as compared to the cells treated either by T0901317 or AM580. Monocytes were obtained from 2 healthy donors with inform consent. Cells were treated in vitro with the vehicle (DMSO 0,1%) or 10ÂµM of the LXR agonist T0901317 for 24 hours. Then after cells were treated for another 24 hour period with or without 100nM of the RARalpha specific agonist AM580.

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Project description:To investigate how LXR activation potentiates expression of Th2 cytokine-dependent genes in primary human macrophages, we pulsed macrophages with synthetic LXR ligand T0901317 then polarized cells to alternatively activated macrophages with IL-4 or IL-13.

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Effect of T0901317, AM580 or T0901317+AM580 on monocyte gene expression

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Liver X receptor beta is the dominant LXR subtype in skeletal muscle

Project description:Liver X receptors (LXRs) are important regulators of cholesterol, lipid and glucose metabolism and have been extensively studied in liver, macrophages and adipose tissue. However, their role in skeletal muscle is not yet fully elucidated and the functional role of each of the LXRM-NM-1 and LXRM-NM-2 subtypes in skeletal muscle is at present unknown. To study the importance of each of the receptor subtypes, myotube cultures derived from wild type (WT), LXRM-NM-1 and LXRM-NM-2 knockout (KO) mice were established. The present study shows that treatment with the unselective LXR agonist T0901317 increased mRNA levels of LXR target genes such as sterol regulatory element-binding transcription factor 1 (SREBF1), fatty acid synthase (FASN), stearoyl-CoA desaturase 1 (SCD1) and ATP-binding cassette transporter A1 (ABCA1) in myotubes established from WT and LXRM-NM-1 KO mice. However, only minor changes in expression level were observed for these genes after treatment with T0901317 in myotubes from LXRM-NM-2 KO mice. Gene expression analysis using Affymetrix NuGO Genechip arrays showed that few other genes than the classical, well known LXR target genes were regulated by LXR in skeletal muscle. Furthermore, functional studies using radiolabeled substrates showed that treatment with T0901317 increased lipogenesis and apoA1 dependent cholesterol efflux, in myotubes from WT and LXRM-NM-1 KO mice, but not LXRM-NM-2 KO mice. The data suggest that the lipogenic effects of LXRs, as well as the LXR-stimulated cholesterol efflux, are mainly mediated by LXRM-NM-2 in skeletal muscle. To study the importance of each of the receptor subtypes, myotube cultures derived from wild type (WT), LXRa and LXRb knockout (KO) mice were established. Sixteen samples were examined. Half the samples were treated with the unselective LXR agonist T0901317.

2010-03-30 | E-GEOD-13192 | biostudies-arrayexpress

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2012-11-07 | E-GEOD-38083 | biostudies-arrayexpress

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