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Series GSE123909 Query DataSets for GSE123909
Status Public on Dec 31, 2020
Title Feeding-induced resistance to acute lethal sepsis is dependent on hepatic BMAL1 and FXR signaling
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Summary Disruption of the circadian rhythm is associated with inflammatory diseases, metabolic syndrome and cancer. In mice, the time of day strongly influences lethality in response to LPS, with survival greatest at the beginning compared to the end of the light cycle (Halberg et al. 1960; Marpegan et al. 2009; Nguyen et al. 2013). Myeloid-cell intrinsic circadian clock components control inflammatory cytokine production (Gibbs et al. 2012; Curtis et al. 2015; Bellet et al. 2013), and metabolic inputs influence lethality in response to LPS (Wang et al. 2016; Weis et al. 2017; Traba et al. 2017), but the relative contributions of these inputs to daily changes in sepsis susceptibility are not known. Here we show that feeding, rather than light, controls time of day dependent LPS sensitivity. Mortality following LPS administration after 12 hours of food deprivation was associated with hypoglycemia, rather than inflammatory cytokine production, independent of the clock regulator BMAL1 expressed in myeloid cells. Deletion of BMAL1 in hepatocytes globally disrupted the transcriptional response to the feeding cycle in the liver and resulted in constitutively high LPS sensitivity. These results show that food, rather than light, is the ‘zeitgeber’ for acute mortality in response to LPS, with a critical role for the hepatocyte-intrinsic circadian clock in integrating nutritional cues to regulate survival in response to innate immune stimuli. Understanding the hepatic molecular programs operational in response to fasting versus fed cues could identify novel pathways that may be targeted to enhance resistance to endotoxemia.
 
Overall design Mice were housed under stable 12 h dark 12 h light conditions and ad libitum feeding for at least a week before access to food was restricted to either the day-time (DF, food from ZT0 to ZT12) or the night-time (NF, food from ZT12 to ZT0). The amount of food was thereby not restricted and normal chow was fed. On day 5 of the time restricted feeding schedule, mice were euthanized at ZT0 or ZT12 and liver samples harvested for RNA isolation.
 
Contributor(s) Geiger SS, Brooks SR
Citation(s) 33980856
Submission date Dec 16, 2018
Last update date May 20, 2021
Contact name Stephen R Brooks
E-mail(s) stephen.brooks@nih.gov
Organization name NIAMS/NIH
Department Biodata Mining and Discovery Section
Street address 50 SOUTH DR, RM 1140
City Bethesda
State/province MD
ZIP/Postal code 20814
Country USA
 
Platforms (1)
GPL21493 Illumina HiSeq 3000 (Mus musculus)
Samples (64)
GSM4983280 KO_DF_0_LPS_F_1
GSM4983281 KO_DF_0_LPS_M_1
GSM4983282 KO_DF_0_LPS_M_2
Relations
BioProject PRJNA510339
SRA SRP173596

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE123909_180718_0153_RNA-Seq_results.gene.rpkm.xlsx 19.5 Mb (ftp)(http) XLSX
GSE123909_180718_0153_untx_WTandKO_ANOVA_RESvsSUSC_9-13-18.xlsx 12.6 Mb (ftp)(http) XLSX
GSE123909_ANOVA_Truly_RvsS_Untx_10-10-18.xlsx 4.3 Mb (ftp)(http) XLSX
SRA Run SelectorHelp
Raw data are available in SRA
Processed data are available on Series record

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