Obesity and associated increased prevalence of non-alcoholic fatty liver (NAFLD) disease is suggested to be positively modulated by a high protein (HP) diet in humans and rodents. The aim was to detect mechanisms by which a HP diet prevents hepatic lipid accumulation by means of transcriptomics. To study the acute and long term effect of a high protein ingestion on hepatic lipid accumulation under both low and high fat (HF) conditions, mice were fed combinations of high (35%) or low (10%) fat and high (50%) or normal (15%) protein diets for 1 or 12 weeks. Body composition, liver fat, VLDL production rate and gene expression were investigated. Differences in metabolic processes and functions in the liver were identified using gene set enrichment analysis on microarray data. Mice fed the HP diets developed less adiposity and decreased hepatic lipid accumulation due a combination of induced processes mainly involved in protein catabolism such as transamination, TCA cycle and oxidative phosphorylation. Feeding a HP diet can successfully prevent the development of NAFLD by using ingested energy for oxidation instead of storage.
Dietary protein affects gene expression and prevents lipid accumulation in the liver in mice.
Sex, Age, Specimen part, Time
View SamplesImmune system homeostasis depends on signals that drive effector (like secretion of pro-inflammatory cytokines like IFNg) and regulatory (like secretion of the anti-inflammatory cytokine IL-10) functions.
The cholesterol biosynthesis pathway regulates IL-10 expression in human Th1 cells.
Specimen part, Subject
View SamplesTo further understand molecular mechanisms underlying skeletal muscle hypertrophy, expression profiles of translationally and transcriptionally regulated genes were characterized following an acute bout of maximally activated eccentric contractions. Experiments demonstrated that translational mechanisms contribute to acute gene expression changes following high resistance contractions with two candidate mRNAs, basic fibroblast growth factor (bFGF) and elongation factor-1 alpha (EF1alpha), targeted to the heavier polysomal fractions after a bout of contractions. Gene profiling was performed using Affymetrix Rat U34A GeneChips with either total RNA or polysomal RNA at one and six hours following contractions. There were 18 genes that changed expression at one hour and 70 genes that were different (60 genes increased:10 genes decreased)at six hours after contractions. The model from this profiling suggests that following high resistance contractions skeletal muscle shares a common growth profile with proliferating cells exposed to serum. This cluster of genes can be classified as "growth" genes and is commonly associated with progression of the cell cycle. However, a unique aspect was that there was induction of a cluster of tumour suppressor or antigrowth genes. We propose that this cluster of "antigrowth" genes is induced by the stress of contractile activity and may act to maintain skeletal muscle in the differentiated state. From the profiling results, further experiments determined that p53 levels increased in skeletal muscle at 6 h following contractions. This novel finding of p53 induction following exercise also demonstrates the power of expression profiling for identification of novel pathways involved in the response to muscle contraction.
Response of rat muscle to acute resistance exercise defined by transcriptional and translational profiling.
No sample metadata fields
View SamplesProbiotic bacteria, specific representatives of bacterial species that are a common part of the human microbiota, are proposed to deliver health benefits to the consumer by modulation of intestinal function via largely unknown molecular mechanisms. To explore in vivo mucosal responses of healthy adults to probiotics, we obtained transcriptomes in an intervention study following a double-blind placebo-controlled cross-over design. In the mucosa of the proximal small intestine of healthy volunteers, probiotic strains from the species Lactobacillus acidophilus, L. casei and L. rhamnosus each induced differential gene regulatory networks and pathways in the human mucosa. Comprehensive analyses revealed that these transcriptional networks regulate major basal mucosal processes, and uncovered remarkable similarity to response profiles obtained for specific bioactive molecules and drugs. This study elucidates how intestinal mucosa of healthy humans perceive different probiotics and provides avenues for rationally designed tests of clinical applications.
Human mucosal in vivo transcriptome responses to three lactobacilli indicate how probiotics may modulate human cellular pathways.
Specimen part
View SamplesMolecular adaptation of the intestinal mucosa occurs during microbial conventionalization to maintain a balanced immune response. However, the genetic regulation of such adaptation is obscure. Here, combined analysis of germ free and conventionalized mice revealed that the major molecular adaptations were initiated at day 4 of conventionalization with a strong induction of innate immune functions followed by stimulation of adaptive immune functions. We identified central regulatory genes and reconstructed a common regulatory network that appeared to be sufficient to regulate the dynamic adaptation of the intestinal mucosa to the colonizing microbiota. The majority of the genes within this regulatory network play roles in mucosal inflammatory diseases in mouse and human. We propose that the identified central regulatory network may serve as a genetic signature for control of intestinal homeostasis in healthy mice and may help to unravel the genetic basis of pathway dysregulation in human intestinal inflammatory diseases.
Temporal and spatial interplay of microbiota and intestinal mucosa drive establishment of immune homeostasis in conventionalized mice.
Sex, Specimen part
View SamplesAttainment of a brown adipocyte cell phenotype in white adipocytes, with their abundant mitochondria and increased energy expenditure potential, is a legitimate strategy for combating obesity. The unique transcriptional regulators of the primary brown adipocyte phenotype are unknown, limiting our ability to promote brown adipogenesis over white. In the present work, we used microarray analysis strategies to study primary preadipocytes, and we made the striking discovery that brown preadipocytes demonstrate a myogenic transcriptional signature, whereas both brown and white primary preadipocytes demonstrate signatures distinct from those found in immortalized adipogenic models. We found a plausible SIRT1-related transcriptional signature during brown adipocyte differentiation that may contribute to silencing the myogenic signature. In contrast to brown preadipocytes or skeletal muscle cells, white preadipocytes express Tcf21, a transcription factor that has been shown to suppress myogenesis and nuclear receptor activity. In addition, we identified a number of developmental genes that are differentially expressed between brown and white preadipocytes and that have recently been implicated in human obesity. The interlinkage between the myocyte and the brown preadipocyte confirms the distinct origin for brown versus white adipose tissue and also represents a plausible explanation as to why brown adipocytes ultimately specialize in lipid catabolism rather than storage, much like oxidative skeletal muscle tissue.
Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages.
No sample metadata fields
View SamplesHeterologous expression of the fungal pathogen Cladosporium fulvum Avr2 in Arabidopsis plants.
The Cladosporium fulvum virulence protein Avr2 inhibits host proteases required for basal defense.
No sample metadata fields
View SamplesSome commensal bacteria stimulate the immune system but do not present specific antigenicity. Such adjuvant effects have been reported for the bacterial species Lactobacillus plantarum. To study in vivo human responses to L. plantarum, a randomised double-blind placebo-controlled cross-over study was performed. Healthy adults were provided preparations of living and heat-killed L. plantarum bacteria, biopsies were taken from the intestinal mucosa and altered transcriptional profiles were analysed. Transcriptional profiles of human epithelia displayed striking differences upon exposure to living L. plantarum bacteria harvested at different growth phases. Modulation of NF-B-dependent pathways was central among the major altered cellular responses. This unique in vivo study shows which cellular pathways are associated with the induction of immune tolerance in mucosal tissues towards common adjuvanticity possessing lactobacilli.
Differential NF-kappaB pathways induction by Lactobacillus plantarum in the duodenum of healthy humans correlating with immune tolerance.
No sample metadata fields
View SamplesClinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to subcategorize patients with subclinical immune activation
Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.
Specimen part
View SamplesPurpose: This study was carried out to determine the consequences of the Rfx2-/- genotype on spermatogenesis in the mouse Methods: RNA was extracted from decapsulated testes of 21 day old mixed background mice of either genotype. Deep sequencing was used to determine quantitative expression of the genomes from independent replicates of each genotype Results: RNA-Seq analysis identified some 105 genes that are down regulated at least 2-fold in Rfx2-/- testes, with ~50 being reduced at least 10-fold Conclusion: Spermatogenesis undergoes complete arrest just prior to the end of the round spermatid period of sperm development in mutant mice. Sequencing results showed that approximately 105 genes were downregulated 2 fold or more in the testes of mutant mice. Comparison of similar studies of targeted mutations in genes for other transcription factor demonstrate that Rfx2 has a large and nearly unique set of genes that depend on it directly or indirectly. A large number of downregulated genes are identified with cilia function. Overall design: Testicular mRNA profiles were determined by deep sequencing using testes from 5 independent wild type and 6 independent Rfx2-/- mice
RFX2 Is a Major Transcriptional Regulator of Spermiogenesis.
No sample metadata fields
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