Hepatic Gene Expression in LIRKO Mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Sudha Biddinger
PROVIDER: E-GEOD-65624 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Control and Liver Insulin Receptor KO mice (LIRKO) were sacrificed in the non-fasted state. RNA was prepared from liver samples and subjected to expression microarray analysis Each array was hybridized with sample derived from 2-3 mice of the same genotype.
2015-02-05 | GSE65624 | GEO
Project description:Little is known about the role of the transcription factor PPAR�/d in liver. Here we set out to better elucidate the function of PPAR�/d in liver by comparing the effect of PPARa and PPAR�/d deletion using whole genome transcriptional profiling and analysis of plasma and liver metabolites. In fed state, the number of genes altered by PPARa and PPAR�/d deletion was similar, whereas in fasted state the effect of PPARa deletion was much more pronounced, consistent with the pattern of gene expression of PPARa and PPAR�/d. Minor overlap was found between PPARa- and PPAR�/d-dependent gene regulation in liver. Pathways upregulated by PPAR�/d deletion were connected to innate immunity. Pathways downregulated by PPAR�/d deletion included lipoprotein metabolism and various pathways related to glucose utilization, which correlated with elevated plasma glucose and triglycerides and reduced plasma cholesterol in PPAR�/d-/- mice. Downregulated genes that may underlie these metabolic alterations included Pklr, Fbp1, Apoa4, Vldlr, Lipg, and Pcsk9, which may represent novel PPAR�/d target genes. In contrast to PPARa-/- mice, no changes in plasma FFA, plasma �-hydroxybutyrate, liver triglycerides and liver glycogen were observed in PPAR�/d-/- mice. Our data indicate a role for PPAR�/d in hepatic glucose utilization and lipoprotein metabolism but not in the adaptive response to fasting. Keywords: Analysis of target gene regulation by using microarrays Pure-bred Sv129 PPARα -/- mice and corresponding wildtype mice were used. Male mice (n=4-5 per group) were either fed or fasted for 24 hours. At the end of the experiment, mice were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%). Blood was collected by orbital puncture, after which the mice were sacrificed by cervical dislocation. Livers were dissected, snap frozen in liquid nitrogen and kept at -80ºC until further analysis. For RNA analyses, tissue from the same part of the liver lobe was used.
2010-06-21 | E-GEOD-17863 | biostudies-arrayexpress
Project description:Metabolic homeostasis in mammals critically depends on the regulation of fasting-induced genes by CREB in the liver. Previous genome-wide analysis has shown that only a small percentage of CREB target genes are induced in response to fasting-associated signaling pathways. The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated. We performed chromatin immunoprecipitation coupled to high-throughput sequencing of CREB in livers from both fasted and re-fed mice. In order to quantitatively compare the extent of CREB-DNA interactions genome-wide between these two physiological conditions we developed a novel, robust analysis method, termed the ‘single sample independence’ (SSI) test that greatly reduced the number of false positive peaks. We found that CREB remains constitutively bound to its target genes in the liver regardless of the metabolic state. Integration of the CREB cistrome with expression microarrays of fasted and re-fed mouse livers and ChIP-seq data for additional transcription factors revealed that the gene expression switches between the fasted and fed states are associated with co-localization of additional transcription factors at CREB sites. Our results support a model in which CREB is constitutively bound to thousands of potential target genes and combinatorial interactions between DNA-binding factors are necessary to achieve the specific transcriptional response of the liver to fasting. Furthermore, our genome-wide analysis identifies thousands of novel CREB target genes in liver, including a previously unknown role for CREB in regulating ER stress genes in response to nutrient influx. Individual livers were collected from 24hr fasted and re-fed mice, with 4 biological replicates per condition. Extracted RNA was hybridized to Agilent two-color arrays, using randomly paired fasted/re-fed replicates.
2013-05-01 | E-GEOD-45731 | biostudies-arrayexpress
Project description:Mice were starved overnight and divided into three groups: a) refed for 30 min b) caged food (not able to reach, but to smell and see food) c) further fasted. The aim of the study was to determine phosphorylation events in the liver in response to visual exposure of food. See more details in the manuscript and Supplementary Tables.
2018-10-31 | PXD005681 | Pride
Project description:In metabolic control, GC signaling acts as a major counter-regulatory system against insulin action, and aberrantly elevated GC activity is tightly linked to major components of the so-called Metabolic Syndrome, including obesity, insulin resistance, hyperglycemia, and systemic dyslipidemia. Here we identify the hepatic induction of the conserved microRNA (miR)-379/410 genomic cluster as a key component of GC/GR-driven metabolic dysfunction in M-bM-^@M-^\diabesityM-bM-^@M-^] Microarray data were utilized to screened for differentially regulated miRNAs between wt and db/db and between wt and GR Knockdown mice For wt vs. db/db: mice were fasted for 24 hours and refed for 6 hours; For GR-dependent miRNAs: mice were treated with rAAV delivering either control or GR-directed miRNA for the knockdown of the GR specifically in the liver.
2014-10-15 | E-GEOD-55245 | biostudies-arrayexpress
Project description:One of the key functions of the mammalian liver is lipid metabolism. During fasting, lipid storage in the liver increases in order to reserve and provide energy for cellular functions. Upon re-feeding, this reserve of lipids is rapidly depleted; this change is visible, as the organelles responsible for lipid storage – lipid droplets (LDs) – drastically decrease in size following re-feeding. Little is known regarding LD proteome, or how it changes during the fasting/re-feeding transition. Our study investigated the hepatic LD proteome and how it changes between fasting and re-feeding conditions. For this purpose, LDs were isolated from 4 month-old C57BL/6 mice after a 24 hour fasting period, or a 24 hour fasting period followed by 6 hours of re-feeding. Proteins isolated from these LDs were subject to SDS-PAGE followed by in-gel trypsinization and LC-MS/MS. We identified a combined total of 941 proteins on hepatic LDs, of which 817 had quantifiable extracted ion chromatograms in at least 2 samples (n=6 total) and were not deemed contaminants. 777 of the 817 proteins were observed in both energetic states, with 33 being uniquely observed in fasted LDs, and 7 being uniquely observed in re-fed LDs.
2018-05-25 | PXD005977 | Pride
Project description:STEAP4 is a plasma membrane metallo-reductase involved in the transport of iron and copper. Recently, STEAP4 was implicated in promoting insulin sensitivity by acting in white adipose tissue (WAT) to control the production of inflammatory cytokines such as IL-6. Indeed, the loss of STEAP4 expression in mice leads to increased production of inflammatory cytokines in visceral WAT and systemic insulin resistance. In this report, we demonstrate that in mouse liver STEAP4 is produced at significant levels and that STEAP4 transcription is induced by IL-6. We further demonstrate that the STEAP4 gene is a direct target of phosphorylated STAT3 in mouse liver. In addition, hepatic STEAP4 expression is regulated by feeding and fasting, and obesity leads to the induction of STEAP4 expression in the liver. Interestingly, the regulation of STEAP4 in both feeding and fasting and the obese state appears to require the transcription factor C/EBPalpha that may act in concert with STAT3 as they both bind to the proximal STEAP4 promoter in vivo. Taken together these data suggest the transcriptional regulation of hepatic STEAP4 may play a critical role in the response to nutritional and inflammatory stress and contribute to the protective effect of STEAP4 in vivo. 10-week old male C57BL6 mice were fasted for 16 h overnight and then given either saline or IL-6 (100 ng/mouse) injections intraperitoneally for 1 h. Mice were euthanized using CO2, and the livers were collected and snap-frozen in liquid nitrogen and stored at -800C until further use.
2010-04-08 | E-GEOD-21060 | biostudies-arrayexpress
Project description:The effect of liver specific deletion of the insulin receptor substrate-1 (Irs1) and/or Irs2 upon gene expression in the fasted and fed liver of mice; and the effect of liver specific Foxo1 deletion in the Irs1 and Irs2 knockout liver during fasting and feeding.
2008-07-31 | E-MEXP-1649 | biostudies-arrayexpress
Project description:Liver mitochondria play a central role in metabolic adaptations to changing nutritional states, yet their dynamic regulation upon anticipated changes in energy state has remained unaddressed. Here, we show that sensory food perception rapidly induces mitochondrial fission in the liver via protein kinase B/AKT-dependent phosphorylation of serine 131 of the Mitochondrial fission factor (MFFS131), and this response is mediated via activation of hypothalamic Pro-opiomelanocortin (POMC)-expressing neurons. A non-phosphorylatable MFFS131G knock-in mutation abrogates AKT-induced mitochondrial fragmentation in vitro. In vivo, MFFS131G knock-in mice display altered liver mitochondrial dynamics upon food perception and refeeding and impaired insulin stimulated suppression of gluconeogenesis. Collectively, we reveal a critical role for rapid activation of a hypothalamic/liver axis to adapt mitochondrial function to anticipated changes of nutritional state in control of hepatic glucose metabolism. The repository contains two LC-MS/MS datasets aiming for the detection of phosphorylated peptides. a) POMC neuron activation and b) time course experiment of fasted, refed and caged food. We assumed that due to the short time (30 min max) that the total protein level remain unchanged.
2024-03-28 | PXD044227 | Pride
Project description:102 postpubertal Holstein dairy heifers were randomly assigned to a fed or fasted treatment. Liver biopsies were performed to obtain tissue from which mRNA was extracted and used for microarray analysis. Transcriptional profiling revealed adaptive mechanisms in response to negative energy balance. Two condition experiment; fed and fasted. Common reference design employed; reference sample consisting of RNA derived from bovine liver, spleen and placental tissue. Biological replicates of 51 Fed (as control) and 51 Fasted (as treatment). One replicate per array. Dye swaps performed on 7 of the 51 fasted treatment group samples, and on 5 of the 51 fed treatment group samples.
2009-05-20 | E-GEOD-16154 | biostudies-arrayexpress