Experiment comparing the liver transcriptome from wild type and KLF10 deficient mice
Kruppel-like factor KLF10 is a link between the circadian clock and metabolism in liver.
Sex, Age, Specimen part, Subject
View SamplesKupffer cells have been implicated in the pathogenesis of various liver diseases. However, their involvement in metabolic disorders of the liver, including fatty liver disease, remains unclear. The present study sought to determine the impact of Kupffer cells on hepatic triglyceride storage and to explore the possible mechanisms involved. To that end, C57Bl/6 mice rendered obese and steatotic by chronic high-fat feeding were treated for 1 week with clodronate liposomes, which cause depletion of Kupffer cells. Loss of expression of marker genes Cd68, F4/80, and Clec4f, and loss of Cd68 immunostaining verified almost complete removal of Kupffer cells from the liver. Also, expression of complement components C1, the chemokine (C-C motif) ligand 6 (Ccl6), and cytokines interleukin-15 (IL-15) and IL-1beta were markedly reduced. Importantly, Kupffer cell depletion significantly decreased liver triglyceride and glucosylceramide levels concurrent with increased expression of genes involved in fatty acid oxidation including peroxisome proliferator-activated receptor alpha (PPARalpha), carnitine palmitoyltransferase 1A (Cpt1alpha), and fatty acid transport protein 2 (Fatp2). Treatment of mice with IL-1beta decreased expression of PPARalpha and its target genes, which was confirmed in primary hepatocytes. Consistent with these data, IL-1beta suppressed human and mouse PPARalpha promoter activity. Suppression of PPARalpha promoter activity was recapitulated by overexpression of nuclear factor kappaB (NF-kappaB) subunit p50 and p65, and was abolished upon deletion of putative NF-kappaB binding sites. Finally, IL-1beta and NF-kappaB interfered with the ability of PPARalpha to activate gene transcription. CONCLUSION: Our data point toward important cross-talk between Kupffer cells and hepatocytes in the regulation of hepatic triglyceride storage. The effect of Kupffer cells on liver triglycerides are at least partially mediated by IL-1beta, which suppresses PPARalpha expression and activity.
Kupffer cells promote hepatic steatosis via interleukin-1beta-dependent suppression of peroxisome proliferator-activated receptor alpha activity.
Sex
View SamplesAnalysis of rapamycin effects on white adipose tissue at gene expression level. The hypothesis tested in the present study was that rapamycin could modify immune cell composition and inflammatory state of the adipose tissue of obese mice.
Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in diet-induced obese mice.
Age, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sex, Specimen part, Treatment
View SamplesIdentified genes deregulated in mouse primary hepatocytes after modulation of expression/activity of FOXA2 and FXR in glucagon or insulin state
The nuclear bile acid receptor FXR is a PKA- and FOXA2-sensitive activator of fasting hepatic gluconeogenesis.
Sex, Specimen part, Treatment
View SamplesSarcoidosis + Follow-up 6 month after
Functional genomics and prognosis in sarcoidosis--the critical role of antigen presentation.
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View SamplesSamples collected from human subjects in clinical trials possess a level of complexity, arising from multiple cell types, that can obfuscate the analysis of data derived from them. Blood, for example, contains many different cell types that are derived from a distinct lineage and carry out a different immunological purpose. Failure to identify, quantify, and incorporate sources of heterogeneity into an analysis can have widespread and detrimental effects on subsequent statistical studies.
Optimal deconvolution of transcriptional profiling data using quadratic programming with application to complex clinical blood samples.
Sex, Specimen part
View SamplesWe assessed the impact of glucose transporter Glut2 gene inactivation in adult mouse liver (LG2KO mice). This suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was normal early after Glut2 inactivation but intolerance developed at later time. This was caused by progressive impairment of glucose-stimulated insulin secretion even though beta-cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinate down-regulation of cholesterol biosynthesis genes in LG2KO mice. This was associated with reduced hepatic cholesterol in fasted mice and a 30 percent reduction in bile acid production. We showed that chronic bile acids or FXR agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls beta-cell glucose competence, through a mechanism that likely depends on bile acid production and action on beta-cells.
Hepatic glucose sensing is required to preserve β cell glucose competence.
Specimen part
View SamplesHydrogen peroxide (H2O2) can act as a signaling molecule that influences various aspects of plant growth and development, including stress signaling and cell death. Catalase deficient plants are pioneering systems which accumulate hydrogen peroxide (H2O2) from peroxisomal origin during photorespiratory challenges. Respiratory burst oxidase homologues D and F are known to participate in intracellular oxidative stress response launched in cat2 mutants (Chaouch et al., 2012). We studied the compared the transcriptional response of cat2 rbohD and cat2 rbohF double mutants versus the cat2 background to further adress their role during photorespiratory stress.
The ROS Wheel: Refining ROS Transcriptional Footprints.
Age
View SamplesHydrogen peroxide (H2O2) is a potent signaling molecule influencing various aspects of plant growth and development. Its limited lifetime and specific production sites in the plant cell necessitate the existence of specialized mechanisms that relay H2O2-encoded information. To discover such mechanisms, we focused on peroxisomal H2O2 production triggered by enhanced photorespiration in Arabidopsis mutants lacking catalase activity (cat2-2), and looked for second-site mutations that attenuate the negative effects (Fv'/Fm' decline and lesion formation) of H2O2 build up. A mutation residing in the GRAS family transcriptional regulator SHORT-ROOT (SHR) was found to underlie the increased performance of cat2-2 knock-outs under photorespiratory stress. In contrast to shr, introduction of the scr mutation in cat2-2 background did not improve the photorespiratory performance of plants lacking peroxisomal catalase. The absence of SHR negatively affected the activity of the photorespiratory enzymes glycolate oxidase and catalase, which was accompanied with elevated glycolate content and inability to accumulate glycine under conditions promoting photorespiration. The transcriptome signature of cat2-2 shr-6 double mutants exposed to photorespiratory stress lacked jasmonate-dependent signaling components, otherwise induced in cat2-2. The photorespiratory phenotype of cat2-2 was found to be modulated by exogenous sugars both in the presence and absence of shr. Taken together, these findings highlight a crucial role for SHR in H2O2 signal transduction and stress tolerance.
The ROS Wheel: Refining ROS Transcriptional Footprints.
Age, Specimen part, Treatment, Time
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