Exacerbated oxidative stress in the fasting liver according to fuel partitioning
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE38695 | GEO | 2015/06/03
SECONDARY ACCESSION(S): PRJNA168445
REPOSITORIES: GEO
Similar Datasets
Project description:White adipose tissue is a central place to energy storage and a major endocrine organ. However, adipose molecular mechanisms have been poorly studied during prolonged fasting. To fill this gap, the aim of this study was to decipher proteomic regulations in rat adipose tissue during phase 2 (lipid mobilization) and phase 3 (protein catabolism) of prolonged fasting compared to the fed state. Specific responses reflecting adipose tissue inflammation, increased fibrinolysis and a possible protein catabolism-related energy saving mechanism were recorded during phase 3. Differences between internal and subcutaneous adipose tissues were essentially related to lipid metabolism, the response to oxidative stress and energy production. These data thus provide a molecular basis of adipose tissue responses according to the fasting stage.
2021-02-24 | PXD010902 | Pride
Project description:Exacerbated oxidative stress in the fasting liver according to fuel partitioning
| PRJNA168445 | ENA
Project description:Background In the postabsorptive state, the portal-drained viscera are a major energy consumer, but a comprehensive overview of the adaptive fasting response in the liver is lacking. Hence, gene-expression profiling, pathway, network and gene-set enrichment analysis and immunohistochemistry were carried out on mouse liver after 0, 12, 24, and 72 hours of fasting. Results Liver weight has fallen to 50% of control after three days of fasting, hepatocyte size was reduced with no apparent increase in apoptosis, while the basic liver structure and metabolic zonnation were preserved. Expression profiling and pathway analysis depicted four master processes, all with response peaking at 24 hours, and all but one decreasing towards 72h. Changes in gene expression were compatible with cellular energy deficiency, and metabolic adaptations were directed at enhanced glucose production, stimulation of lipid catabolism and ketone body synthesis, and strongly augmented ATP production. Consequently, the expression of genes involved in oxidative and endoplasmic reticulum stress response was increased. In addition, urea cycle genes were strongly upregulated during whole duration of fasting, in spite no obvious increase in amino-acid catabolism. Major physiological change upon continued fasting was restoration of glycogen reserves, but with reverse localization, demonstrating utilization of different glycogenic precursor compared to the fed controls. Conclusion The changes in liver gene expression indicate a rapid onset of generating glucose and ketone bodies during short, and a return to near normal situation in prolonged fasting. The reason apparently lies in glycogen repletion, due to late fasting glucose production by (gut and) kidney. Keywords: fasting response, time course
2008-10-23 | GSE10653 | GEO
Project description:Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARα target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPARα in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPARα activity. In addition, activation of mouse PPARα regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPARα, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPARα agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPARα and that plasma vanin activity could serve as a readout of changes in PPARα activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting. Livers of wild type and vanin-1 knockout mice that were fed or fasted for 24h were subjected to gene expression analysis
2014-04-24 | E-GEOD-51712 | biostudies-arrayexpress
Project description:Smith2013 - Regulation of Insulin Signalling by Oxidative Stress
The model describes insulin signalling (in rodent adipocytes), which includes in addition to the core pathway, the transcriptional feedback through the Forkhead box type O (FOXO) transcription factor and interaction with oxidative stress.
This model is described in the article:
Computational modelling of the regulation of Insulin signalling by oxidative stress.
Smith GR, Shanley DP.
BMC Syst Biol. 2013 May 24;7:41.
Abstract:
BACKGROUND:
Existing models of insulin signalling focus on short term dynamics, rather than the longer term dynamics necessary to understand many physiologically relevant behaviours. We have developed a model of insulin signalling in rodent adipocytes that includes both transcriptional feedback through the Forkhead box type O (FOXO) transcription factor, and interaction with oxidative stress, in addition to the core pathway. In the model Reactive Oxygen Species are both generated endogenously and can be applied externally. They regulate signalling though inhibition of phosphatases and induction of the activity of Stress Activated Protein Kinases, which themselves modulate feedbacks to insulin signalling and FOXO.
RESULTS:
Insulin and oxidative stress combined produce a lower degree of activation of insulin signalling than insulin alone. Fasting (nutrient withdrawal) and weak oxidative stress upregulate antioxidant defences while stronger oxidative stress leads to a short term activation of insulin signalling but if prolonged can have other effects including degradation of the insulin receptor substrate (IRS1) and FOXO. At high insulin the protective effect of moderate oxidative stress may disappear.
CONCLUSION:
Our model is consistent with a wide range of experimental data, some of which is difficult to explain. Oxidative stress can have effects that are both up- and down-regulatory on insulin signalling. Our model therefore shows the complexity of the interaction between the two pathways and highlights the need for such integrated computational models to give insight into the dysregulation of insulin signalling along with more data at the individual level.A complete SBML model file can be downloaded from BIOMODELS (https://www.ebi.ac.uk/biomodels-main) with unique identifier MODEL1212210000.Other files and scripts are available as additional files with this journal article and can be downloaded from https://github.com/graham1034/Smith2012_insulin_signalling.
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2013-09-06 | BIOMD0000000474 | BioModels
Project description:We sequenced mRNA from 4 liver samples of the large yellow croaker (Larimichthys crocea) taken from thermal stress treatment fish, normal temperature treatment fish, cold stress treatment fish and fasting stress treatment fish, respectively, to investigate the transcriptome and comparative expression profiles of the large yellow croaker liver undergoing thermal stress, cold stress and fasting. Liver mRNA profiles of control group (LB2A), thermal stress group (LC2A), cold stress group (LA2A) and 21-day fasting group (LF1A) were generated by RNA-seq, using Illumina HiSeq 2000.
2015-08-06 | E-GEOD-67756 | biostudies-arrayexpress
Project description:We sequenced mRNA from 4 liver samples of the large yellow croaker (Larimichthys crocea) taken from thermal stress treatment fish, normal temperature treatment fish, cold stress treatment fish and fasting stress treatment fish, respectively, to investigate the transcriptome and comparative expression profiles of the large yellow croaker liver undergoing thermal stress, cold stress and fasting.
2015-08-06 | GSE67756 | GEO
Project description:Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of hepatic fat oxidation that serves as an energy source during starvation. Vanin-1 has been described as a putative PPARα target gene in liver, but its function in hepatic lipid metabolism is unknown. We investigated the regulation of vanin-1, and total vanin activity, by PPARα in mice and humans. Furthermore, the function of vanin-1 in the development of hepatic steatosis in response to starvation was examined in Vnn1 deficient mice, and in rats treated with an inhibitor of vanin activity. Liver microarray analyses reveals that Vnn1 is the most prominently regulated gene after modulation of PPARα activity. In addition, activation of mouse PPARα regulates hepatic- and plasma vanin activity. In humans, consistent with regulation by PPARα, plasma vanin activity increases in all subjects after prolonged fasting, as well as after treatment with the PPARα agonist fenofibrate. In mice, absence of vanin-1 exacerbates the fasting-induced increase in hepatic triglyceride levels. Similarly, inhibition of vanin activity in rats induces accumulation of hepatic triglycerides upon fasting. Microarray analysis reveal that the absence of vanin-1 associates with gene sets involved in liver steatosis, and reduces pathways involved in oxidative stress and inflammation. We show that hepatic vanin-1 is under extremely sensitive regulation by PPARα and that plasma vanin activity could serve as a readout of changes in PPARα activity in human subjects. In addition, our data propose a role for vanin-1 in regulation of hepatic TG levels during fasting.
2014-04-24 | GSE51712 | GEO
Project description:Intensive oxidative stress occurs during high-fat-diet-induced hepatic fat deposition, suggesting a critical role for redox signaling in liver metabolism. Intriguingly, lines of evidence show that fasting could also result in redox profile changes, largely through reduced oxidant and/or increased anti-oxidant levels. However, a comprehensive landscape of redox-modified hepatic substrates is lacking, thus hindering our understanding of liver metabolic homeostasis. In this study, we employed a proteomic approach which combines iodoTMT and nanoLC-MS/MS to quantitatively probe the effects of high-fat-feeding and fasting on in vivo redox-based cysteine modifications. Collectively, we identified 1258 redox cysteine sites in 603 proteins and quantified 846 sites in 403 proteins.
2022-03-03 | PXD006612 | Pride
Project description:Background; In the postabsorptive state, the portal-drained viscera are a major energy consumer, but a comprehensive overview of the adaptive fasting response in the liver is lacking. Hence, gene-expression profiling, pathway, network and gene-set enrichment analysis and immunohistochemistry were carried out on mouse liver after 0, 12, 24, and 72 hours of fasting. Results; Liver weight has fallen to 50% of control after three days of fasting, hepatocyte size was reduced with no apparent increase in apoptosis, while the basic liver structure and metabolic zonnation were preserved. Expression profiling and pathway analysis depicted four master processes, all with response peaking at 24 hours, and all but one decreasing towards 72h. Changes in gene expression were compatible with cellular energy deficiency, and metabolic adaptations were directed at enhanced glucose production, stimulation of lipid catabolism and ketone body synthesis, and strongly augmented ATP production. Consequently, the expression of genes involved in oxidative and endoplasmic reticulum stress response was increased. In addition, urea cycle genes were strongly upregulated during whole duration of fasting, in spite no obvious increase in amino-acid catabolism. Major physiological change upon continued fasting was restoration of glycogen reserves, but with reverse localization, demonstrating utilization of different glycogenic precursor compared to the fed controls. Conclusion; The changes in liver gene expression indicate a rapid onset of generating glucose and ketone bodies during short, and a return to near normal situation in prolonged fasting. The reason apparently lies in glycogen repletion, due to late fasting glucose production by (gut and) kidney. Experiment Overall Design: Male FVB mice (Charles River, Maastricht, The Netherlands) were housed at 20-22°C, 50-60% humidity, a 12 hours light/dark cycle, and food and water ad libitum. At 6 weeks of age, mice were fasted by removing chow for up to 72 hours before sacrifice (n = 6 per group). All animals were sacrificed between 9:00 and 10:00 a.m. by cervical dislocation. The liver was removed quickly, weighed, snap-frozen in liquid N2, and stored at -80°C. Total intestinal RNA was extracted from frozen tissue using TRIzol (Invitrogen), followed by a cleanup through a RNeasy column (Qiagen). The quality of RNA was assessed with the RNA 6000 Nano LabChip® Kit in an Agilent 2100 bioanalyzer (Agilent Technologies, Palo Alto, USA). The 60-mer Mouse Development (22K) Oligo Microarray G4120A (Agilent) was used. Three arrays per experimental condition were used. Per microarray, 20 μg mRNA, pooled from 2 livers, was reverse transcribed with Cy3-labelled dCTP (Perkin Elmer, Boston, USA), using the Agilent Fluorescent Direct Label Kit. Cy5-labeled cDNA produced from RNA pooled from livers of 6 fed animals served as the common reference across all arrays. Hybridized cDNAs were detected with Agilentâ??s dual-laser microarray slide scanner. The data were retrieved with Agilentâ??s Feature Extraction software 6.1.1.
2008-11-21 | E-GEOD-10653 | biostudies-arrayexpress