Project description:We used microarray analysis to identify differences in gene expression levels in heart following an 18h (overnight) fast in WT control and KLF15-null mice Heart tissue was isolated from 3-4 month old, 18h-fasted WT and KLF15-null male mice for RNA extraction and hydridization on Affymetrix microarrays
Project description:We used microarray analysis to identify differences in gene expression levels, in liver and in quadriceps skeletal muscle, between 18h (overnight) fasted WT control and Kruppel-like factor 15 (KLF15)-null mice. Experiment Overall Design: Liver and skeletal muscle (quadriceps) tissues were isolated from 4-5 month old, 18h-fasted WT and KLF15-null female mice for RNA extraction and hybridization on Affymetrix microarrays.
Project description:We used microarray analysis to identify differences in gene expression levels, in liver and in quadriceps skeletal muscle, between 18h (overnight) fasted WT control and Kruppel-like factor 15 (KLF15)-null mice. Keywords: comparative expression analysis, fasted state
Project description:We used microarray analysis to identify differences in gene expression levels in heart following an 18h (overnight) fast in WT control and KLF15-null mice
Project description:The ketogenic diet has been successful in promoting weight loss among patients that have struggled with weight gain. This is due to the cellular switch in metabolism that utilizes liver-derived ketone bodies for the primary energy source rather than glucose. Fatty acid transport protein 2 (FATP2) is highly expressed in liver, small intestine, and kidney where it functions in both the transport of exogenous long chain fatty acids (LCFA) and in the activation to CoA thioesters of very long chain fatty acids (VLCFA). We have completed a multi-omic study of FATP2-null (Fatp2-/-) mice maintained on a ketogenic diet (KD) or paired control diet (CD), with and without a 24-hour fast (KD-fasted and CD-fasted) to address the impact of deleting FATP2 under high-stress conditions. Control (wt/wt) and Fatp2-/- mice were maintained on their respective diets for 4-weeks. Afterwards, half the population was sacrificed while the remaining were fasted for 24-hours prior to sacrifice. We then performed paired-end RNA-sequencing on the whole liver tissue to investigate differential gene expression. The differentially expressed genes mapped to ontologies such as the metabolism of amino acids and derivatives, fatty acid metabolism, protein localization, and components of the immune system’s complement cascade, and were supported by the proteome and histological staining.
Project description:this dataset encompasses the cardiac transcriptomic changes elicited in myocardial tissues of 4months-old mice at 4 hours after a single ZT0 prednisone (1mg/kg i.p.) injection, or vehicle, in cardiomyocyte-KLF15-WT versus cardiomyocyte-KLF15-KO conditions (inducible, tamoxifen-driven ablation right prior to drug pulse).
Project description:Regulation between the fed and fasted state in mammals is partially controlled by peroxisome proliferator activated receptor-alpha (PPAR-alpha). Expression of the receptor is high in liver, heart and skeletal muscle, but decreases with age. A combined 1H NMR spectroscopy and GC-MS metabolomic approach has been used to examine metabolism in liver, heart, skeletal muscle and adipose tissue in PPAR-alpha null mice and wild type controls during ageing between 3-13 months. For the PPAR-alpha-null mouse multivariate statistics highlighted hepatic steatosis, reductions in the concentrations of glucose and glycogen in both liver and muscle tissue, and profound changes in lipid metabolism in each tissue, reflecting known expression targets of the PPAR-alpha receptor. Hepatic glycogen and glucose also decreased with age for both genotypes. These findings indicate the development of age related hepatic steatosis in the PPAR-alpha-null mouse, with the normal metabolic changes associated with ageing exacerbating changes associated with genotype. Furthermore, the combined metabolomic and multivariate statistics approach provides a robust method for examining the interaction between age and genotype. </p> The GC-MS assay for this study can be found in the MetaboLights study MTBLS314.
Project description:Sustained cardiac stress promotes the transition from an adaptive response to heart failure. Understanding of mechanisms governing this transition will assist in identifying targets that prevent this progression. Our study revealed age-specific transcriptional functions mediated by KLF15 that are crucial for cardiac homeostasis. We report that postnatally, KLF15 continuously activates cardiac metabolism, but represses pathological, hypertrophic pathways associated with cardiomyocyte de-differentiation and endothelial cell (EC) remodeling in an age-dependent manner. Our integrative genomic and transcriptomic analyses identified novel target genes directly bound, and either activated or repressed by KLF15 in vivo in the adult heart. We identified a cooperative program inducing aberrant EC remodeling, caused by a reduction of KLF15 and a concomitant activation of Wnt signaling. Within this program, we further identified a so far uncharacterized cardiac gene - Shisa3, which is expressed in the developing heart and is upregulated in cardiac hypertrophy, ischemia and failure. Importantly, we demonstrate that the KLF15- and Wnt co-dependent, SHISA regulation occurs also in the human myocardium. Altogether, our results unraveled and characterized a previously unknown cardiac gene Shisa3, and attributed its significance to EC homeostasis of the adult heart, controlled by KLF15-Wnt dynamics. Purpose: The aim of this study was to compare transcriptome profiles (RNA-seq) of heart tissue with a WT or KO Klf15 locus at different murine ages - postnatal day10 (p10), 4-week-old and 20-week-old mice. Methods: Cardiac tissue total RNA profiles for different groups were obtained using deep sequencing, in triplicates, using Illumina HiSeq4000. The sequence reads that passed quality filters were analyzed at the transcript isoform level with TopHat, followed by DESeq2. qPCR validation was performed using TaqMan and SYBR Green assays. Conclusions: Our study represents the first detailed analysis of the processes triggered upon Klf15 loss in hearts of different murine postnatal ages, which was so far not investigated. We report that this Klf15 loss first triggers Wnt canonical pathway activation, followed by activation of the non-canonical Wnt components, culminating in heart failure.
Project description:By comparing the ChIPseq signal of REV_ERBa in control (Flox) and cardiomyocytic KLF15 knockout (cKO), we identified the KLF15 dependent REV-ERBa binding and repression in the heart. We further compared the differential binding sites to KLF15 binding site, using a FLAG tagged cardiomyocytic transgenic (cTG1) mice.