Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [ChIP-Seq]

ABSTRACT: The discovery of FoxO1 as an effector of insulin action on gene expression filled a gap in our knowledge of insulin signaling. The metabolic impact of hepatic FoxO1 has been demonstrated in genetic mouse models showing that FoxO1 inhibition can reverse diabetes. However, the gamut of FoxO1 targets is unknown, due to the lack of robust genome-wide chromatin occupancy data. To elucidate the genomic architecture of the FoxO1 effect on liver metabolism, we integrated genome-wide ChIP-seq and RNA-seq. During the physiological transition from fasting to refeeding, hepatic FoxO1 translocated from the nucleus to the cytoplasm. At the same time points, cistrome analysis demonstrated that 60% of FoxO1 target sites were cleared by refeeding. RNA-seq from mice following acute liver-specific FoxO1 ablation allowed us to integrate the data in a comprehensive FoxO1 regulome. We identified four distinct classes of FoxO1 targets. Class I targets are enriched in genes regulating cell homeostasis, have FoxO1 sites clustered in promoters and do not show regulation with fasting/refeeding. Class II is comprised of canonical FoxO1 metabolic targets coordinately regulated with other fasting-inducible TFs, such as PPARA, CREB, and GR through promoters. Class III is enriched in glucose metabolic genes regulated through active enhancers, as detected by H3K4me1 and H3K27ac histone marks. Class IV is comprised of triglyceride (TG) and lipoprotein metabolism genes, regulated through intron sites, and characterized by an uneven response to fasting/refeeding regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE151544 | GEO | 2022/05/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Characterization of chromatin and gene expression changes during fasting and refeeding in mouse liver [RNA-Seq]

Project description:The discovery of FoxO1 as an effector of insulin action on gene expression filled a gap in our knowledge of insulin signaling. The metabolic impact of hepatic FoxO1 has been demonstrated in genetic mouse models showing that FoxO1 inhibition can reverse diabetes. However, the gamut of FoxO1 targets is unknown, due to the lack of robust genome-wide chromatin occupancy data. To elucidate the genomic architecture of the FoxO1 effect on liver metabolism, we integrated genome-wide ChIP-seq and RNA-seq. During the physiological transition from fasting to refeeding, hepatic FoxO1 translocated from the nucleus to the cytoplasm. At the same time points, cistrome analysis demonstrated that 60% of FoxO1 target sites were cleared by refeeding. RNA-seq from mice following acute liver-specific FoxO1 ablation allowed us to integrate the data in a comprehensive FoxO1 regulome. We identified four distinct classes of FoxO1 targets. Class I targets are enriched in genes regulating cell homeostasis, have FoxO1 sites clustered in promoters and do not show regulation with fasting/refeeding. Class II is comprised of canonical FoxO1 metabolic targets coordinately regulated with other fasting-inducible TFs, such as PPARA, CREB, and GR through promoters. Class III is enriched in glucose metabolic genes regulated through active enhancers, as detected by H3K4me1 and H3K27ac histone marks. Class IV is comprised of triglyceride (TG) and lipoprotein metabolism genes, regulated through intron sites, and characterized by an uneven response to fasting/refeeding regulation.

2022-05-24 | GSE151545 | GEO

Integrated Control of Hepatic Lipogenesis vs. Glucose Production Requires FoxO Transcription Factors

Project description:Insulin integrates hepatic glucose and lipid metabolism, directing nutrients to storage as glycogen and triglyceride. In type 2 diabetes, levels of the former are low and the latter are exaggerated, posing a pathophysiologic and therapeutic conundrum. A branching model1 of insulin signaling, with FoxO1 presiding over glucose production2-5 and Srebp–1c regulating lipogenesis,6-8 provides a potential explanation. Here we illustrate an alternative mechanism that integrates glucose production and lipogenesis under the unifying control of FoxO. Liver–specific ablation of three FoxOs (L–FoxO1,3,4) prevents the induction of glucose–6–phosphatase and the repression of glucokinase during fasting, thus increasing lipogenesis at the expense of glucose production. We document a similar pattern in the early phases of diet-induced insulin resistance, and propose that FoxOs are required to enable the liver to direct nutritionally derived carbons to glucose vs. lipid metabolism. Our data underscore the heterogeneity of hepatic insulin resistance during progression from the metabolic syndrome to overt diabetes, and the conceptual challenge of designing therapies that curtail glucose production without promoting hepatic lipid accumulation. We used microarrays to detail the change of gene expression in liver after knocking out FoxO1,3 and 4. Liver tissue samples were collected from hepatocyte- specific triple FoxO(1,3, and 4) KO and their littermates control (WT) mice after fasting (22 h) or refeeding (4 h). Gene expression was analyzed by microarray. Mice were on a mixed background of C57BL/6J and 129.

2014-08-20 | E-GEOD-60527 | biostudies-arrayexpress

Chromatin IP sequencing of the nuclear factor HMGB1 in livers from mice after a metabolic stress either induced by a 12-week high fat diet consumption or a fasting (6hours)-refeeding (8hours) challenge.

Project description:To unveil HMGB1 DNA occupancy in livers of mice after a metabolic stress either induced by a 12-week high fat diet consumption or a fasting (6hours)-refeeding (8hours) challenge. Challenges known to generate a robust activation of hepatic lipogenesis and liver steatosis.

2022-03-31 | E-MTAB-11543 | biostudies-arrayexpress

Gene expression profiling using cDNA microarray of HMGB1fl/fl and HMGB1ΔHep liver samples from mice subjected to a 12 week-HFD regimen or a Fasting/Refeeding challenge

Project description:To unveil any gene expression difference induced by hepatocyte specific-Hmgb1 gene deletion in mice after a metabolic stress either induced by a 12-week high fat diet consumption or a fasting (6hours)-refeeding (8hours) challenge. Challenges known to generate a robust activation of hepatic lipogenesis and liver steatosis.

2022-03-31 | E-MTAB-11541 | biostudies-arrayexpress

Effects of extensive fasting and subsequent feeding on hepatic transcription

Project description:Temporally restricted feeding has a profound effect on the circadian clock. Fasting and feeding paradigms are known to influence hepatic transcription. This dataset shows the dynamic effects of refeeding mice after a 24hour fasting period.

2009-11-23 | GSE13063 | GEO

Fasting/fed/refeeding RNAseq experiment conducted on mice with xenografted human livers.

Project description:Human hepatic gene regulations by fasting and refeeding in a mouse model with humanized liver generated from a single donor were reported.

2021-01-06 | GSE130525 | GEO

Liver and Plasma metaboites for 13C-glucose load in wild type, LIRKO and LIRFKO mice

Project description:FoxO proteins are major targets of insulin action. To better define the role of FoxO1 in mediating insulin effects in the liver, we generated liver-specific insulin receptor knockout (LIRKO) and IR/FoxO1 double knockout (LIRFKO) mice. Here we show that LIRKO mice are severely insulin resistant based on glucose, insulin and C-peptide levels, and glucose and insulin tolerance tests, and genetic deletion of hepatic FoxO1 reverses these effects. 13C-glucose and insulin clamp studies indicate that regulation of both hepatic glucose production (HGP) and glucose utilization is impaired in LIRKO mice, and these defects are also restored in LIRFKO mice corresponding to changes in gene expression. We conclude that (1) inhibition of FoxO1 is critical for both direct (hepatic) and indirect effects of insulin on HGP and utilization, and (2) extrahepatic effects of insulin are sufficient to maintain normal whole-body and hepatic glucose metabolism when liver FoxO1 activity is disrupted. Research is published: http://www.nature.com/ncomms/2015/150512/ncomms8079/full/ncomms8079.html

2015-06-10 | ST000198 | MetabolomicsWorkbench

Penguin plasma LC-MSMS - The Safety Limits Of An Extended Fast: Lessons from a Non-Model Organism

Project description:While safety of fasting therapy is debated in humans, extended fasting occurs routinely and safely in wild animals. To do so, food deprived animals like breeding penguins anticipate the critical limit of fasting by resuming feeding. To date, however, no molecular indices of the physiological state that links spontaneous refeeding behaviour with fasting limits had been identified. Blood proteomics and physiological data reveal here that fasting-induced body protein depletion is not unsafe “per se”. Indeed, incubating penguins only abandon their chick/egg to refeed when this state is associated with metabolic defects in glucose homeostasis/fatty acid utilization, insulin production and action, and possible renal dysfunctions. Our data illustrate how the field investigation of “exotic” models can be a unique source of information, with possible biomedical interest.

2017-01-02 | PXD004808 | Pride

Transcription profiling of Drosophila after fasting

Project description:In fasted mammals, glucose homeostasis is maintained through activation of the cAMP responsive CREB coactivator TORC2, which stimulates the gluconeogenic program in concert with the forkhead transcription factor FOXO1. Here we show that starvation also triggers TORC activation in Drosophila, where it maintains energy balance by promoting the expression of CREB target genes in the brain. TORC mutant flies have reduced glycogen and lipid stores, and they are sensitive to starvation as well as oxidative stress. Neuronal TORC expression rescued starvation and oxidative stress sensitivity as well as CREB target gene expression in TORC mutants. During refeeding, increases in insulin signaling inhibited TORC activity in wild type flies by stimulating the Salt Inducible Kinase 2 (SIK2)-mediated phosphorylation and subsequent degradation of TORC. Depletion of neuronal SIK2 increased TORC activity and enhanced resistance to starvation and oxidative stress in adult flies. As disruption of insulin signaling, either by ablation of insulin-producing cells (IPCs) or by mutation of the insulin receptor adaptor gene chico, also increased TORC activity, our results illustrate the importance of an insulin-regulated pathway in brain that promotes energy balance in Drosophila. Experiment Overall Design: Male fly heads were collected after 24h fasting, and RNA was extracted using RNAeasy kit.

2008-10-20 | E-GEOD-10546 | biostudies-arrayexpress

Comparison of hepatic gene expression in response to fasting or 2 week high fat diet

Project description:The metabolic syndrome represents a cluster of well-documented risk factors for the development of type 2 diabetes and cardiovascular disease. Next to visceral obesity, dyslipidemia and insulin resistance, excessive triglyceride accumulation in the liver has been implicated to play a role in the development of the metabolic syndrome. To investigate the underlying molecular changes leading to hepatic steatosis we performed microarray analysis on livers of mice either fasted over night or fed a high fat diet for 2 Weeks. We analysed 7 500 genes and subsequently performed a pathway analysis to identify changes in hepatic genes in both models. Fasting induced a high number of differentially expressed hepatic genes, resulting in an change towards an energy saving phenotype. In contrast only a small number of genes were differentially expressed after high fat diet. Fasting promoted gluconeogenesis and b-oxidation, strongly suppressed cholesterol synthesis and activated pathways to preserve hepatic function. High fat diet induced steatosis was accompanied by the activation of the stearoyl-CoA desaturase and the lipogenic transcription factor Srebp-1c, both implicated in the development of hepatic insulin resistance. These changes reflect the activation of different gene expression programs in response to plasma lipid overload. Keywords: Diet intervention Two conditions, fasting and high fat diet. 5 biological replicates for comparison of high fat diet versus fasting and controls versus high fat diet, 4 biological replicates for the comparison of controls versus fasting. All biological replicates are performed as technical replicates in the form of a dye-swap. Total number of arrays hybridises is therefore 28.

2011-04-02 | E-GEOD-8576 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data