Transcriptome signature of white adipose tissue, liver, and skeletal muscle in 24 hours fasted mice (C57Bl/6J)
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Andreas Prokesch
PROVIDER: E-GEOD-46495 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The endoplasmic reticulum (ER) is an organelle associated with lipid metabolism. However, the involvement of the ER in nutritional status-dependent energy homeostasis is largely unknown. The results of this study demonstrate that IRE-1, an ER protein known to be involved in the unfolded protein response, and HSP-4, an ER chaperone, regulate expression of the novel fasting-induced lipases FIL-1 and FIL-2, which induce fat granule hydrolysis upon fasting in C. elegans. RNAi and ectopic expression experiments demostrated that FIL-1 and FIL-2 are both necessary and sufficient for fasting-induced fat granule breakdown. Failure of ire-1 and hsp-4 mutant animals to hydrolyze fat granules during starvation impaired their motility, which was rescued by glucose supplementation of their media, implicating the importance of ire-1/hsp-4-dependent lipolysis for energy supply from stored fat during fasting. Taken together, these data suggest that the ER-resident proteins IRE-1 and HSP-4 are key nutritional sensors that modulate expression of inducible lipases to maintain whole-body energy homeostasis in C. elegans. Synchronized L4 worms were divided into well-fed and 6 hours fasted samples for RNA extraction and hybridization on an Agilent microarray.
2010-05-08 | E-GEOD-15656 | biostudies-arrayexpress
Project description:One of the key functions of the mammalian liver is lipid metabolism. During fasting, lipid storage in the liver increases in order to reserve and provide energy for cellular functions. Upon re-feeding, this reserve of lipids is rapidly depleted; this change is visible, as the organelles responsible for lipid storage – lipid droplets (LDs) – drastically decrease in size following re-feeding. Little is known regarding LD proteome, or how it changes during the fasting/re-feeding transition. Our study investigated the hepatic LD proteome and how it changes between fasting and re-feeding conditions. For this purpose, LDs were isolated from 4 month-old C57BL/6 mice after a 24 hour fasting period, or a 24 hour fasting period followed by 6 hours of re-feeding. Proteins isolated from these LDs were subject to SDS-PAGE followed by in-gel trypsinization and LC-MS/MS. We identified a combined total of 941 proteins on hepatic LDs, of which 817 had quantifiable extracted ion chromatograms in at least 2 samples (n=6 total) and were not deemed contaminants. 777 of the 817 proteins were observed in both energetic states, with 33 being uniquely observed in fasted LDs, and 7 being uniquely observed in re-fed LDs.
2018-05-25 | PXD005977 | Pride
Project description:The aim of this study was to compare the effects of cocoa butter and safflower oil on hepatic transcript profiles, lipid metabolism and insulin sensitivity in healthy rats. Cocoa butter-based high-fat feeding for three days did not affect plasma total triglyceride (TG) levels or TG-rich VLDL particles or hepatic insulin sensitivity, but changes in hepatic gene expression were induced that might lead to increased lipid synthesis, lipotoxicity, inflammation and insulin resistance if maintained. Safflower oil increased hepatic β-oxidation, was beneficial in terms of circulating TG-rich VLDL particles, but led to reduced hepatic insulin sensitivity. The effects of safflower oil on hepatic gene expression were partly overlapping with those exerted by cocoa butter, but fewer transcripts from anabolic pathways were altered. Increased hepatic cholesterol levels and increased expression of hepatic CYP7A1 and ABCG5 mRNA, important gene products in bile acid production and cholesterol excretion, were specific effects elicited by safflower oil only. Common effects on gene expression included increased levels of p8, DIG-1 IGFBP-1 and FGF21, and reduced levels of SCD-1 and SCD-2. This indicates that a lipid-induced program for hepatic lipid disposal and cell survival was induced by three days of high-fat feeding, independent on the lipid source. Based on the results, we speculate that hepatic TG infiltration leads to reduced expression of SCD-1, which might mediate either neutral, beneficial or unfavourable effects on hepatic metabolism upon high-fat feeding, depending on which fatty acids were provided by the diet. Keywords: Hepatic gene expression Two-condition experiment. Biological replicates: 4 male rat livers from rats on a standard diet, 4 male rat livers from rats on a cocoa butter diet, 4 male rat livers from rats on a high-fat (safflower oil) diet. One replicate per array.
2010-05-18 | E-GEOD-13936 | biostudies-arrayexpress
Project description:There is growing evidence that energy metabolism and insulin action are regulated by mechanisms that follow a diurnal rhythm and it has been proposed that defects in Akt signalling are associated with the pathophysiology of metabolic disease. It is therefore important to investigate these parameters under physiology of the free-living state. We therefore examined the insulin action in muscle of chow or high fat, high sucrose diet-fed (HFHS) rats during the normal diurnal cycle. HFHS animals displayed hyperinsulinemia, however had reduced systemic glucose disposal and impaired muscle glucose uptake during the feeding period. Proteomics and phosphoproteomics was performed over the diurnal cycle in chow and HFHS rats.
2019-05-20 | PXD010242 | Pride
Project description:Metabolic homeostasis in mammals critically depends on the regulation of fasting-induced genes by CREB in the liver. Previous genome-wide analysis has shown that only a small percentage of CREB target genes are induced in response to fasting-associated signaling pathways. The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated. We performed chromatin immunoprecipitation coupled to high-throughput sequencing of CREB in livers from both fasted and re-fed mice. In order to quantitatively compare the extent of CREB-DNA interactions genome-wide between these two physiological conditions we developed a novel, robust analysis method, termed the M-bM-^@M-^Xsingle sample independenceM-bM-^@M-^Y (SSI) test that greatly reduced the number of false positive peaks. We found that CREB remains constitutively bound to its target genes in the liver regardless of the metabolic state. Integration of the CREB cistrome with expression microarrays of fasted and re-fed mouse livers and ChIP-seq data for additional transcription factors revealed that the gene expression switches between the fasted and fed states are associated with co-localization of additional transcription factors at CREB sites. Our results support a model in which CREB is constitutively bound to thousands of potential target genes and combinatorial interactions between DNA-binding factors are necessary to achieve the specific transcriptional response of the liver to fasting. Furthermore, our genome-wide analysis identifies thousands of novel CREB target genes in liver, including a previously unknown role for CREB in regulating ER stress genes in response to nutrient influx. CREB ChIP-seq was performed on mouse liver from fasted and re-fed mice, using 5 separate biological replicates for each condition. GR and C/EBP(beta) ChIP-seq were performed as single replicates on ad-lib fed mice.
2013-05-01 | E-GEOD-45674 | biostudies-arrayexpress
Project description:Fasting is the process of metabolic adaption to food deprivation that is taking place in most organisms, e.g. during the daily resting phase in mammals. Furthermore, in biomedical research fasting is used in most metabolic studies to synchronize nutritional states of study subjects. Because there is a lack of standardization for this procedure, we need a deeper understanding of the dynamics and the molecular players in fasting. In this study we investigated the transcriptome signature of white adipose tissue, liver, and skeletal muscle in 24 hours fasted mice (and chow fat controls) using Affymetrix whole-genome microarrays.
2013-11-04 | GSE46495 | GEO
Project description:Objectives Intermittent fasting is an effective dietary intervention to combat metabolic disease. Here, we explore the adipose depot specific response to every-other-day fasting (EODF) in mice to identify mechanisms that underly the beneficial effects. Methods Male C57BL/6J mice were placed on a 12-day EODF or ad libitum diet, after which tissues were harvested including visceral (vWAT) and subcutaneous (scWAT) white adipose tissue, as well as brown adipose tissue (BAT), which was then analysed by unbiased mass spectrometry-based proteomics. Results After EODF treatment, pathway enrichment analysis of our dataset showed that both WAT depots showed increased mitochondrial protein content, with scWAT also showing increased UCP1, but mitochondrial protein content was decreased in BAT. This effect on mitochondria is correlated to the increased abundance of proteins involved in glycolysis, pyruvate metabolism, the TCA cycle and fatty acid synthesis in both WAT depots. Furthermore, EODF-treated mice downregulated the lipolysis pathway in vWAT including a 5-fold decrease in the abundance of the beta3 adrenergic receptor (ADRB3). Enrichment analysis lso revealed that vWAT of EODF treated mice had significantly reduced ECM proteins, which lowers the inflammatory potential of this organ. Our adipose depot proteomic survey also allowed us to identify depot-enriched protein expression, such as the vWAT enrichment for the AKAP12 protein related to PKA signalling that was down-regulated by EODF treatment. Conclusions These findings show how the adipose depots have adapted to the EODF regime to preserve the lipid store, with the most striking changes occurring in the vWAT depot to downregulate the lipolysis pathway and induce expression of pathways needed for fatty acid synthesis. This substrate cycling and reduced inflammatory potential of the adipose tissue may contribute to the improved insulin sensitivity observed in these animals.
2022-10-12 | PXD020255 | Pride
Project description:Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles including the endoplasmic reticulum (ER). This communication is important in thermogenic adipocytes to increase energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood. Herein, stress-induced cytosolic chaperone PPID (peptidyl-prolyl isomerase D/cyclophilin 40/Cyp40) drives OMM insertion of the mitochondrial import receptor TOM70 regulating body temperature and weight in obese mice, and respiratory/thermogenic function in brown adipocytes. PPID PPIase activity and C-terminal tetratricopeptide repeats (TPR), which show specificity towards TOM70 core and C-tail domains, facilitate OMM insertion. Our results provide an unprecedented role for ER-stress-activated chaperones in controlling energy metabolism through a selective OMM protein insertion mechanism with implications in adaptation to cold temperatures and high-calorie diets.
2024-10-02 | PXD054182 | Pride
Project description:Outer mitochondrial membrane (OMM) proteins communicate with the cytosol and other organelles including the endoplasmic reticulum (ER). This communication is important in thermogenic adipocytes to increase energy expenditure that controls body temperature and weight. However, the regulatory mechanisms of OMM protein insertion are poorly understood. Herein, stress-induced cytosolic chaperone PPID (peptidyl-prolyl isomerase D/cyclophilin 40/Cyp40) drives OMM insertion of the mitochondrial import receptor TOM70 regulating body temperature and weight in obese mice, and respiratory/thermogenic function in brown adipocytes. PPID PPIase activity and C-terminal tetratricopeptide repeats (TPR), which show specificity towards TOM70 core and C-tail domains, facilitate OMM insertion. Our results provide an unprecedented role for ER-stress-activated chaperones in controlling energy metabolism through a selective OMM protein insertion mechanism with implications in adaptation to cold temperatures and high-calorie diets.
2024-10-02 | PXD055263 | Pride
Project description:Metabolic homeostasis in mammals critically depends on the regulation of fasting-induced genes by CREB in the liver. Previous genome-wide analysis has shown that only a small percentage of CREB target genes are induced in response to fasting-associated signaling pathways. The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated. We performed chromatin immunoprecipitation coupled to high-throughput sequencing of CREB in livers from both fasted and re-fed mice. In order to quantitatively compare the extent of CREB-DNA interactions genome-wide between these two physiological conditions we developed a novel, robust analysis method, termed the ‘single sample independence’ (SSI) test that greatly reduced the number of false positive peaks. We found that CREB remains constitutively bound to its target genes in the liver regardless of the metabolic state. Integration of the CREB cistrome with expression microarrays of fasted and re-fed mouse livers and ChIP-seq data for additional transcription factors revealed that the gene expression switches between the fasted and fed states are associated with co-localization of additional transcription factors at CREB sites. Our results support a model in which CREB is constitutively bound to thousands of potential target genes and combinatorial interactions between DNA-binding factors are necessary to achieve the specific transcriptional response of the liver to fasting. Furthermore, our genome-wide analysis identifies thousands of novel CREB target genes in liver, including a previously unknown role for CREB in regulating ER stress genes in response to nutrient influx. Individual livers were collected from 24hr fasted and re-fed mice, with 4 biological replicates per condition. Extracted RNA was hybridized to Agilent two-color arrays, using randomly paired fasted/re-fed replicates.
2013-05-01 | E-GEOD-45731 | biostudies-arrayexpress