The purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodeled the hepatic transcriptome of F2 female rats
Paternal high-fat diet transgenerationally impacts hepatic immunometabolism.
Sex, Specimen part
View SamplesThe purpose of this study was to investigate whether grandpaternal high-fat diet (HFD) transgenerationally remodels the transcriptome of skeletal muscle
Grandpaternal-induced transgenerational dietary reprogramming of the unfolded protein response in skeletal muscle.
Sex, Specimen part
View SamplesHigh fat feeding is deleterious for skeletal muscle metabolism, while exercise has well documented beneficial effects for these same metabolic features. To identify the genomic mechanisms by which exercise ameliorates some of the deleterious effects of high fat feeding, we investigated the transcriptional and epigenetic response of human skeletal muscle to 9 days of a high-fat diet (HFD) alone (Sed-HFD) or in combination with resistance exercise (Ex-HFD), using genome-wide profiling of gene expression (by RNA-seq) and DNA methylation (by Reduced Representation Bisulfite Sequencing). HFD markedly induced expression of immune and inflammatory genes which was not attenuated by Ex. In contract, Ex markedly remodelled expression of genes associated with muscle growth and structure. We detected marked DNA methylation changes following HFD alone and in combination with Ex. Among the genes that showed significant association between DNA methylation changes and gene expression were glycogen phosphorylase, muscle associated (PYGM), which was epigenetically regulated in both groups, and angiopoiten like 4 (ANGPTL4), which was regulated only following Ex. We conclude that Short-term Ex does not prevent HFD-induced inflammatory response, but provokes a genomic response that may preserve skeletal muscle from atrophy. Epigenetic adaptation provides important mechanistic insight into the gene specific regulation of inflammatory and metabolic processes in human skeletal muscle. Overall design: Sedentary or exercising human subjects undergo high-fat diet intervention.
Transcriptomic and epigenetic responses to short-term nutrient-exercise stress in humans.
Specimen part, Subject, Time
View SamplesThe purpose of this study was to investigate whether paternal high-fat diet (HFD) transgenerationally remodels the epigenome of spermatozoa to alter metabolism in the F1 and F2 generation offspring
High-fat diet reprograms the epigenome of rat spermatozoa and transgenerationally affects metabolism of the offspring.
Sex, Specimen part
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients.
Sex, Specimen part, Disease stage
View SamplesType 2 diabetes is a complex disease associated with many underlying pathomechanisms. Epigenetic regulation of gene expression by DNA methylation has become increasingly recognized as an important component in the etiology of type 2 diabetes. We performed genome-wide methylome and transcriptome analysis in liver from severely obese patients with or without type 2 diabetes to discover aberrant pathways underlying the development of insulin resistance. We identified hypomethylation of five key genes involved in hepatic glycolysis, de novo lipogenesis and insulin resistance with concomitant increased mRNA expression and protein content. The CpG-site within the ATF-motif was hypomethylated in four of these genes in liver of non-diabetic and type 2 diabetic obese patients, suggesting epigenetic regulation of transcription by altered ATF-DNA binding. In conclusion, severely obese non-diabetic and type 2 diabetic patients have distinct alterations in the hepatic methylome and transcriptome and genes controlling glucose and lipid metabolism are hypomethylated at a regulatory site. Thus, obesity may epigenetically reprogram the liver towards increased lipid production and exacerbate the development of insulin resistance.
Altered DNA methylation of glycolytic and lipogenic genes in liver from obese and type 2 diabetic patients.
Sex, Specimen part, Disease stage
View SamplesBovine papillomavirus (BPV) is the causative agent of papillomatosis in cattle. The disease causes cutaneous and mucosal lesions that can be minimized or lead to the appearance of malignant tumors. This study aims to identify possible molecular mechanisms that are behind the pathological processes associated with bovine papillomatosis through the identification of genes related to the development of the lesions. For this, next-generation RNA sequencing was used to assess differentially expressed genes in infected by BPV and non-infected bovines. Three animals with papillomatosis lesion and three without papillomatosis lesion were studied. The Galaxy platform was used to analyze the data generated by the sequencing. The Illumina output files were converted to FASTQ format. Quality evaluation was performed using FastQC and the sequence quality cut was performed using Trimmomatic. TopHat and Bowtie were used to map and align the reads with the reference genome. The abundance of the expressed genes was verified using Cuffilinks. Cuffdiff was used for differential expression analysis. Functional annotation of the differentially expressed genes was performed using Gene Ontology (GO) databases. RNA-sequencing generated a total of 121,722,238 of reads. In the gene expression analysis, a total of 13,421 genes expressed were identified and of these 1343 were differentially expressed. The functional annotation of differentially significant genes showed that many genes presented functions or they were related to metabolic pathways associated with the progression of papillomatosis lesions and cancer development in cattle. Although more studies are needed, this is the first study that focused on a large-scale evaluation of gene expression associated with the BPV infection, which is important to identify possible mechanisms regulated by the host genes that are necessary the development of the lesion Overall design: Analysis of three BPV infected and three BPV non-infected samples
Comparative transcriptomic analysis of bovine papillomatosis.
Age, Specimen part, Treatment, Subject
View SamplesWe performed the circadian transcriptome analysis using the skeletal muscle from sedentary and exercised mice either in the early rest phase (ZT3) or in the early active phase (ZT15). By the combination with circadian transcriptomic and metabolomic analysis, we revealed time-of-day-dependent remodeling of circadian muscular metabolic pathways involved in glucose and glycerol metabolism after exercise. We found that only exercise in the early active phase elevates the levels of genes encoding glycolytic enzymes followed by the activation of fatty acid oxidation, branched-chain amino acid catabolism and ketogenesis/ketosis. This study demonstrates that time-of-day is a critical factor to modulate the impact of exercise on metabolic pathways within skeletal muscle. Overall design: Skeletal muscles from sedentary (sham-exercise) mice and mice subjected to acute treadmill exercise either in the early rest phase (ZT3) or in the early active phase (ZT15) were harvested after 0, 4, 8, 12, 16, and 20 hours after exercise or sham-exercise treatment.
Time of Exercise Specifies the Impact on Muscle Metabolic Pathways and Systemic Energy Homeostasis.
Sex, Specimen part, Cell line, Treatment, Subject
View SamplesThe development of CRISPR-Cas systems for targeting DNA and RNA in diverse organisms has transformed biotechnology and biological research. Moreover, the CRISPR revolution has highlighted bacterial adaptive immune systems as a rich and largely unexplored frontier for discovery of new genome engineering technologies. In particular, the class 2 CRISPR-Cas systems, which use single RNA-guided DNA-targeting nucleases such as Cas9, have been widely applied for targeting DNA sequences in eukaryotic genomes. Here, we report DNA-targeting and transcriptional control with class I CRISPR-Cas systems. Specifically, we repurpose the effector complex from type I variants of class 1 CRISPR-Cas systems, the most prevalent CRISPR loci in nature, that target DNA via a multi-component RNA-guided complex termed Cascade. We validate Cascade expression, complex formation, and nuclear localization in human cells and demonstrate programmable CRISPR RNA (crRNA)-mediated targeting of specific loci in the human genome. By tethering transactivation domains to Cascade, we modulate the expression of targeted chromosomal genes in both human cells and plants. This study expands the toolbox for engineering eukaryotic genomes and establishes Cascade as a novel CRISPR-based technology for targeted eukaryotic gene regulation. Overall design: Examination of transcriptome-wide changes in gene expression with Cascade-mediated activation of endogenous genes.
Targeted transcriptional modulation with type I CRISPR-Cas systems in human cells.
Specimen part, Cell line, Subject
View SamplesThe global prevalence of obesity is increasing across age and gender. The rising burden of obesity in young people contributes to the early emergence of type 2 diabetes. Having one parent obese is an independent risk factor for childhood obesity. While the detrimental impact of diet-induced maternal obesity on offspring is well established, the extent of the contribution of obese fathers is unclear, as is the role of non-genetic factors in the casual pathway. Here we show that paternal high fat diet exposure programmed -cell dysfunction in their F1 female offspring. Chronic high fat diet consumption in Sprague Dawley fathers led to increased body weight, adiposity, impaired glucose tolerance and insulin sensitivity. Relative to controls, their female offspring had lower body weight at day-1, increased pubertal growth rate, impaired insulin secretion and glucose tolerance, in the absence of obesity or increased adiposity. Paternal high fat diet was observed to alter gene expression of pancreatic islet genes in adult female offspring (P < 0.001); affected functional clusters includes calcium ion binding, insulin, apoptosis, Wnt and cell cycle organ/system development. This is the first reported study in mammals describing non-genetic, intergenerational transmission of metabolic sequelae of high fat diet from father to offspring. These findings support a role of fathers in metabolic programming of offspring and form a framework for further studies.
Chronic high-fat diet in fathers programs β-cell dysfunction in female rat offspring.
Sex
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