Fasting response of mouse brain
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE72987 | GEO | 2015/11/14
SECONDARY ACCESSION(S): PRJNA295531
REPOSITORIES: GEO
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Project description:Short-term fasting elicits beneficial effects in mice and humans, including protection from chemotherapy toxicity, but the involved mechanisms are not well understood. We collected blood samples from healthy human volunteers and mice before and after 36 or 24 hours of fasting, respectively, to measure fatty acid composition of erythrocyte membranes, circulating miRNAs, and RNA expression at PBMCs. In both mice and humans, fasting affected the proportion of polyunsaturated versus saturated and monounsaturated fatty acids at the erythrocyte membrane. Also, fasting significantly reduced the expression at PBMCs of insulin signaling-related genes, including the SREBP lipid-metabolizing pathway, in correlation with changes in membrane fatty acids. We tested the relevance of these fatty acid homeostasis parameters using a complete platform to monitor chemotherapy toxicity in mice. When fasted for 24 hours before and 24 hours after administration of the chemotherapeutic drug oxaliplatin, mice showed a strong protection from kidney, liver, heart and bone marrow toxicity. Importantly, the newly discovered fasting parameters defined two clearly separated groups of individuals that accurately predicted a differential protection from chemotherapy toxicity. Our results reveal a novel mechanism of fasting associated with fatty acids homeostasis, and provide novel biomarkers of fasting to predict fasting-mediated protection from chemotherapy toxicity.
2022-06-12 | GSE173241 | GEO
Project description:The effects of fasting have been studied extensively, predominantly on isolated processes, within a specific organ. No comprehensive study of the adaptations was available for different organs, let alone interrelating them, which left the understanding of the body’s orchestration of fasting response limited. The gene expression profiles of brain, small intestine, kidney, liver and skeletal muscle were therefore studied in mice subjected to short, moderate and prolonged fasting. Functional category enrichment, network, and text-mining analyses were employed to scrutinize the overall adaptive response, aiming to identify responsive pathways, processes and networks, and their regulation. The implicated processes did not follow the accepted carbohydrate-lipid-protein succession of energy substrates expenditure. Instead, they were activated simultaneously in different organs during the whole duration of fasting. The most prominent changes occurred in lipid and steroid metabolism, especially in the liver and kidney, which showed biochemically similar, orchestrated responses. They were accompanied by suppression of the immune response and cell turnover, particularly in the small intestine, tied in with increased proteolysis in the muscle. Enhanced defence against oxidative damage, obvious in all the organs, was the top reaction of the brain, otherwise shown to be extremely well protected from starvation. The major transcription regulators of fasting response in different organs were FoxO transcription factors, AP-1, p53, cMyc, Sp1, EGF and HNF4α. The revealed interorgan interactions between metabolic, inflammatory and cell turnover responses are essential when designing strategies to treat the starvation affected individuals, while stressing the significance of using complimentary bioinformatics tools in the high-throughput data analysis. 6 week-old male FVB mice were fasted for 0, 12, 24, 48 or 72 hours before sacrifice (N = 5 per group). From each mouse total RNA was isolated from five organs - liver, small intestine, kidney, brain, and calf muscle. Five microarrays per experimental condition (five tissues, five timepoints) were performed. We used a common reference design. The single common-reference sample was a pool of equal amounts of RNA from all the samples investigated, including additional samples from 5 mice that were fasted for 48 hours and supplemented with vitamin B complex after 24 and 36 hours of fasting.
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Project description:This study utilized AgRP+/- and AgRP-/- mice either under fed or 30h fasted conditions, to reveal genes that are regulated by fasting and AgRP.
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Project description:Short-term fasting protects mice from lethal doses of chemotherapy through undetermined mechanisms. Herein, we demonstrate that fasting preserves small intestinal (SI) architecture by maintaining SI stem cell viability and SI barrier function following exposure to high-dose etoposide. Nearly all SI stem cells were lost in fed mice, whereas fasting promoted sufficient SI stem cell survival to preserve SI integrity after etoposide treatment. Lineage tracing identified multiple SI stem cell populations, marked by Lgr5, Bmi1 or HopX expression, that contributed to fasting-induced survival. DNA repair and DNA damage response genes were elevated in SI stem/progenitor cells of fasted etoposide-treated mice, which importantly correlated with faster resolution of DNA double strand breaks and less apoptosis. Thus, fasting preserved SI stem cell viability as well as SI architecture and barrier function suggesting that fasting may reduce host toxicity in patients undergoing dose intensive chemotherapy. Intestines were harvested 3 h post-etoposide injection, flushed with PBS, and then flushed with ice-cold Methacarn (60% methanol, 30% chloroform, 10% acetic acid) to fix the tissue while preserving RNA integrity. Fixed intestines were rinsed with 70% ethanol, embedded in 2% agar followed by paraffin embedding. Sections were deparrafinized and dehydrated through xylene and an increasing gradient of ethanol. Laser capture microdissection was performed using the Acturus PixCell IIe, with the following settings: spot size power 80, duration 1 ms, repeat 0.2 s, target 0.150 V, current 1.82 mA. RNA was isolated from the CapSure HS LCM Caps (Applied Biosystem) using the PicoPure RNA Isolation kit (Applied Biosystems). All RNA samples were treated with DNaseI (Qiagen). Four biological replicates were used for each of the following treatments: Fasted Etoposide, Fed Etoposide. Each group had 2 male and 2 females samples. 4-6 week old Lgr5EGFP-IRES-CreERT2/+ mice were dosed with 80mg/kg etoposide (i.v.).
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Project description:Caloric restriction is considered to be anti-inflammatory. In this study we examined the effect of fasting on peripheral leukocyte populations. We found that short-term fasting affects metabolic and pro-inflammatory activity of monocytes and decreases numbers of circulating monocytes. For this study, we sorted hepatocytes from fed and fasted mice, monocytes from bone marrow from fed and fasted mice, and monocytes from bone marrow from wildtype and Ccr2-deficient mice.
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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.
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2009-11-23 | E-GEOD-13063 | biostudies-arrayexpress
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.
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