Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat: Liver Transcriptome Changes in Study 2
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PROVIDER: PRJNA510542 | ENA |
REPOSITORIES: ENA
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Project description:Purpose: The purpose of this study is to measure the changes in liver transcriptome in response to short-term fasting between 7 and 13 h where the rats were dosed with 2 ml/kg of saline vehicle at 0 h Methods: Total RNA was isolated from the liver, using TRIzol Reagent (Thermo Fisher Scientific, Waltham, MA) and the direct-zol RNA Mini Prep kit (Zymo Research, Irvine, CA). The isolated RNA samples were then submitted to the Vanderbilt University Medical Center VANTAGE Core (Nashville, TN) for RNA quality determination and sequencing. Total RNA quality was assessed using a 2100 Bioanalyzer (Agilent, Santa Clara, CA). At least 200 ng of DNase-treated total RNA with high RNA integrity was used to generate poly-A-enriched mRNA libraries, using KAPA Stranded mRNA sample kits with indexed adaptors (Roche, Indianapolis, IN). Library quality was assessed using the 2100 Bioanalyzer (Agilent), and libraries were quantitated using KAPA library Quantification kits (Roche). Pooled libraries were subjected to 75-bp paired-end sequencing according to the manufacturer’s protocol (Illumina HiSeq3000, San Diego, CA). Results: No genes were were found to be differentially expressed with a false discovery rate less than 0.1 Conclusions: There were no significant changes in liver gene expression between 7 and 13 h of fasting
2019-03-19 | GSE123987 | GEO
Project description:Purpose: The purpose of this study is to measure the changes in liver transcriptome in response to short-term fasting between 5 and 10 h where the rats were dosed with 6 ml/kg of polyethylene glycol vehicle at 0 h Methods: Total RNA was isolated from the liver, using TRIzol Reagent (Thermo Fisher Scientific, Waltham, MA) and the direct-zol RNA Mini Prep kit (Zymo Research, Irvine, CA). The isolated RNA samples were then submitted to the Vanderbilt University Medical Center VANTAGE Core (Nashville, TN) for RNA quality determination and sequencing. Total RNA quality was assessed using a 2100 Bioanalyzer (Agilent, Santa Clara, CA). At least 200 ng of DNase-treated total RNA with high RNA integrity was used to generate poly-A-enriched mRNA libraries, using KAPA Stranded mRNA sample kits with indexed adaptors (Roche, Indianapolis, IN). Library quality was assessed using the 2100 Bioanalyzer (Agilent), and libraries were quantitated using KAPA library Quantification kits (Roche). Pooled libraries were subjected to 75-bp single-end sequencing according to the manufacturer’s protocol (Illumina HiSeq3000, San Diego, CA). Results: No genes were were found to be differentially expressed with a false discovery rate less than 0.1 Conclusions: There were no significant changes in liver gene expression between 5 and 10 h of fasting
2019-03-19 | GSE123935 | GEO
Project description:Purpose: The purpose of this study is to measure the changes in liver transcriptome in response to short-term fasting between 5 and 10 h where the rats were dosed with 2 ml/kg of corn oil vehicle at 0 h Methods: Total RNA was isolated from the liver, using TRIzol Reagent (Thermo Fisher Scientific, Waltham, MA) and the direct-zol RNA Mini Prep kit (Zymo Research, Irvine, CA). The isolated RNA samples were then submitted to the Vanderbilt University Medical Center VANTAGE Core (Nashville, TN) for RNA quality determination and sequencing. Total RNA quality was assessed using a 2100 Bioanalyzer (Agilent, Santa Clara, CA). At least 200 ng of DNase-treated total RNA with high RNA integrity was used to generate poly-A-enriched mRNA libraries, using KAPA Stranded mRNA sample kits with indexed adaptors (Roche, Indianapolis, IN). Library quality was assessed using the 2100 Bioanalyzer (Agilent), and libraries were quantitated using KAPA library Quantification kits (Roche). Pooled libraries were subjected to 150-bp paired-end sequencing according to the manufacturer’s protocol (Illumina NovaSeq6000, San Diego, CA). Results: Conclusions: There were 100 genes that could be mapped to the rat metabolic network iRno, with significant changes in expression between 5 and 10 h of fasting in the top 10% by effect size parameter b (b > 0.6).
2019-03-19 | GSE124004 | GEO
Project description:Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat: Liver Transcriptome Changes in Study 1
| PRJNA510348 | ENA
Project description:Network Modeling of Liver Metabolism to Predict Plasma Metabolite Changes During Short-Term Fasting in the Laboratory Rat: Liver Transcriptome Changes in Study 3
| PRJNA510426 | ENA
Project description:Transcriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight and backfat and increased serum concentrations of non-esterified fatty acid and urea. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE, q value less than 0.05). MC4R genotype did not affect gene expression, body weight, backfat depth, and any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that both liver and fat down-regulated energetically costly processes such as lipid and steroid synthesis and up-regulated efficient energy utilization pathways. Fasting increased expression of genes in involved in glucose sparing pathways in liver and extracellular matrix pathways in adipose tissue. Within the DE genes, transcription factors (TF) that regulate many DE genes were identified, confirming the involvement of TF that are known to regulate fasting response and implicating additional TF that are not known to be involved in energy homeostatic responses. Interestingly, estrogen receptor 1 transcriptionally controls fasting induced genes in fat that are involved in cell matrix morphogenesis. Our findings indicate a transcriptional response to fasting in two key metabolic tissues of pigs that was corroborated by changes in blood metabolites; and involvement of novel putative transcriptional regulators in the immediate adaptive response to fasting.
2009-04-20 | GSE13528 | GEO
Project description:Transcriptional profiling coupled with blood metabolite analyses were used to identify porcine genes and pathways that respond to a fasting treatment or to a D298N missense mutation in the melanocortin-4 receptor (MC4R) gene. Gilts (12 homozygous for D298 and 12 homozygous for N298) were either fed ad libitum or fasted for 3 days. Fasting decreased body weight and backfat and increased serum concentrations of non-esterified fatty acid and urea. In response to fasting, 7,029 genes in fat and 1,831 genes in liver were differentially expressed (DE, q value less than 0.05). MC4R genotype did not affect gene expression, body weight, backfat depth, and any measured serum metabolite concentration. Pathway analyses of fasting-induced DE genes indicated that both liver and fat down-regulated energetically costly processes such as lipid and steroid synthesis and up-regulated efficient energy utilization pathways. Fasting increased expression of genes in involved in glucose sparing pathways in liver and extracellular matrix pathways in adipose tissue. Within the DE genes, transcription factors (TF) that regulate many DE genes were identified, confirming the involvement of TF that are known to regulate fasting response and implicating additional TF that are not known to be involved in energy homeostatic responses. Interestingly, estrogen receptor 1 transcriptionally controls fasting induced genes in fat that are involved in cell matrix morphogenesis. Our findings indicate a transcriptional response to fasting in two key metabolic tissues of pigs that was corroborated by changes in blood metabolites; and involvement of novel putative transcriptional regulators in the immediate adaptive response to fasting. Experiment Overall Design: Gilts (n=24; 12 wildtype and 12 homozygous for D298N) were either fed ad libitum or fasted for 3 days in a completely randomized complete block design with a 2x2 factorial treatment structure.
2009-04-25 | E-GEOD-13528 | biostudies-arrayexpress
Project description:The liver-a central metabolic organ that integrates whole-body metabolism to maintain glucose and fatty-acid regulation, and detoxify ammonia-is susceptible to injuries induced by drugs and toxic substances. Although plasma metabolite profiles are increasingly investigated for their potential to detect liver injury earlier than current clinical markers, their utility may be compromised because such profiles are affected by the nutritional state and the physiological state of the animal, and by contributions from extrahepatic sources. To tease apart the contributions of liver and non-liver sources to alterations in plasma metabolite profiles, here we sought to computationally isolate the plasma metabolite changes originating in the liver during short-term fasting. We used a constraint-based metabolic modeling approach to integrate central carbon fluxes measured in our study, and physiological flux boundary conditions gathered from the literature, into a genome-scale model of rat liver metabolism. We then measured plasma metabolite profiles in rats fasted for 5-7 or 10-13 h to test our model predictions. Our computational model accounted for two-thirds of the observed directions of change (an increase or decrease) in plasma metabolites, indicating their origin in the liver. Specifically, our work suggests that changes in plasma lipid metabolites, which are reliably predicted by our liver metabolism model, are key features of short-term fasting. Our approach provides a mechanistic model for identifying plasma metabolite changes originating in the liver.
| S-EPMC6405515 | biostudies-literature
Project description:water only fasting changes gut microbiota
| PRJEB9337 | ENA
Project description:Intermittent fasting (IF) increases lifespan, decreases metabolic disease phenotypes, and cancer risk in model organisms, but the mechanisms mediating these effects are not fully characterized. In particular, the altered transcriptional programming has yet to be defined in key fasting responsive tissues such as liver from animals undergoing intermittent fasting. In this study, we employed every-other-day-fasting (EODF) in mice and high-resolution proteome analysis of liver and blood plasma as a screening tool to identify key regulated pathways with comparison to ad libitum fed animals. We observed many changes in the liver proteome abundance profile that were distinct from those observed after a single bout of fasting. Key among these were the induction by EODF of de novo lipogenesis (DNL) and cholesterol biosynthesis pathway enzymes, which were mirrored by related metabolite changes such as increased triacylglycerides and HMG-CoA in EODF liver of fed mice. Paradoxically, we also observed the up-regulation of mitochondrial proteins associated with fatty-acid beta oxidation including ACOT2, which is known to accelerate this pathway in vivo. The most surprising observation was the EODF-mediated 16-fold down-regulation of alpha-1-antitrypsin (SERPINA1E) in liver, which is an abundant plasma protein made exclusively in this tissue. Plasma proteome analysis confirmed a 3-fold decrease in SERPINA1E after 2 weeks of EODF among other significant changes such as increased levels of APOA4, a finding in common with previous human EODF intervention studies. We determined that in liver the SREBP1c and HNF4A transcription factors were playing a major role in the up-regulation of lipid/cholesterol synthesis and down-regulation of AAT, respectively. Further characterization of HNF4A function suggested a global inhibition of its ability to bind promoters of target genes in livers from EODF animals, which we hypothesize is mediated by either increased linoleic acid binding, or post translational modifications of HNF4A protein in EODF animal liver tissue. Together these data provide a comprehensive Omics resource highlighting the key changes observed during the intermittent fasting response in a model animal.
2020-04-30 | PXD015553 | Pride