Repeated fasting events sensitize chromatin and gene expression to support augmented ketogenesis
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA877234 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21440900_1.fastq.gz | Fastqsanger.gz | |||
| SRR21440900_2.fastq.gz | Fastqsanger.gz | |||
| SRR21440901_1.fastq.gz | Fastqsanger.gz | |||
| SRR21440901_2.fastq.gz | Fastqsanger.gz | |||
| SRR21440902_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 49 |
Similar Datasets
Project description:Mammals evolved to withstand frequent fasting periods due to hepatic production of glucose and ketone bodies. Because the fasting response is transcriptionally-regulated, we asked whether enhancer dynamics impose a transcriptional program during recurrent fasting and whether this produces effects distinct from a single fasting bout. We found that mice undergoing alternate-day fasting (ADF) respond to a following fasting bout profoundly differently from mice first experiencing fasting. Hundreds of genes enabling ketogenesis are ‘sensitized’, i.e. induced more strongly by fasting following ADF. Enhancers regulating these genes are also sensitized and harbor increased binding of the major ketogenic transcription factor. ADF mice show augmented ketogenesis and their sensitized enhancers are covalently marked with ketone body residues. Thus, we found that past fasting events are ‘remembered’ in hepatocytes, sensitizing their enhancers to the next fasting bout and augmenting ketogenesis. Our findings shed light on transcriptional regulation mediating adaptation to repeated environmental signals.
2024-11-18 | GSE212776 | GEO
Project description:A Macrophage-Hepatocyte Glucocorticoid Receptor Axis Coordinates Fasting Ketogenesis
| PRJNA622550 | ENA
Project description:Ketone bodies, intermediates in energy metabolism and signaling, have attracted significant attention due to their role in health and disease. We performed around the clock study on ketone bodies and ketogenesis with mice on different diets. We found that caloric restriction, a dietary intervention that improves metabolism and longevity, induced high amplitude circadian rhythms in blood βOHB. The blood βOHB rhythms resulted from rhythmic ketogenesis in the liver controlled by the interaction between the circadian clock and PPAR transcriptional networks. This interaction results in transcriptional reprogramming of in beta-oxidation and ketogenesis enzymes. The reprogramming is impaired in circadian clock mutant mice. The circadian clock gated ketogenesis contributes to the diet impact on health and longevity.
2022-08-31 | GSE211975 | GEO
Project description:Dietary restriction (DR) has multiple beneficial effects on health and longevity and can also improve the efficacy of certain therapies. Diets used to instigate DR are diverse and the corresponding response is not uniformly measured. We compared the systemic and liver-specific transcriptional response to intermittent fasting (IF) and commercially available fasting-mimicking diet (FMD) after short and long-term use in C57BL/6J mice. We show that neither DR regimen causes observable adverse effects in mice. The weight loss was limited to 20% and was quickly compensated during refeeding days. The slightly higher weight loss upon FMD versus IF correlated with stronger fasting response assessed by lower glucose levels and higher ketone body, free fatty acids, and especially FGF21 concentrations in blood. RNA sequencing demonstrated similar transcriptional programs in the liver after both regimens, with PPARα signalling as top enriched pathway, while on individual gene level FMD more potently increased gluconeogenesis-related, and PPARα and p53 target gene expression compared to IF. Repeated IF induced similar transcriptional responses as acute IF. However, repeated cycles of FMD resulted in blunted expression of genes involved in ketogenesis and fatty acid oxidation. Short-term FMD causes more pronounced changes in blood parameters and slightly higher weight loss than IF, while both activate similar pathways (particularly PPARα signalling) in the liver. On individual gene level FMD induces a stronger transcriptional response, whereas cyclic application blunts transcriptional upregulation of fatty acid oxidation and ketogenesis only in FMD. Hence, our comparative characterization of IF and FMD protocols renders both as effective DR regimens and serves as resource in the fasting research field.
2024-10-23 | GSE279842 | GEO
Project description:Pulmonary ketogenesis promotes tolerance to bacterial infection
| PRJNA839615 | ENA
Project description:Short-term starvation (STS or fasting) provides protection to normal cells, mice, and possibly patients from a variety of chemotherapy drugs, but the possibility that it may also protect tumor cells renders its translational potential uncertain. Here we show that fasting cycles can be as effective as toxic chemotherapy drugs, and increase chemotherapy efficacy in the treatment of melanoma, glioma, breast cancer, and neuroblastoma. In vitro, STS sensitizes to chemotherapy 15 of the 17 cancer cell lines tested. In combination with chemotherapy STS results in a synergistic 20-fold increase in DNA damage, increased phosphorylation of pro-aging genes AKT and S6 kinase, reduced expression of stress resistance transcription factors FOXO3a and NFkB, elevated superoxide, and activated caspase-3; all changes not observed in normal tissues. Several of these effects are linked to the activity of heme oxygenase 1 (HO-1), whose modulation was sufficient to regulate chemotherapy-dependent cell death in breast cancer cells. These studies suggest that multiple fasting cycles have the potential to replace certain toxic chemotherapy drugs and to sensitize a wide range of tumors to chemotherapy. To obtain an unbiased view of the gene expression changes occurring in cancer cells in response to fasting, we performed genome-wide microarray analyses, using Illumina's Sentrix MouseRef-8 v2 Expression BeadChips (Illumina, San Diego, CA), on the subcutaneous 4T1 breast cancer tumor mass, heart, muscle and liver tissues from balb-c mice that were either fasted for 48 hours or fed an ad lib diet. Three mice from each of the starvation and the ad lib fed groups were used for the array studies.
2012-03-21 | E-GEOD-28556 | biostudies-arrayexpress
Project description:Elucidation of metabolic flux and switch is fundamental for understanding of CD8+ memory T (Tm) cell development. Glycogen, an intracellular carbon reservoir, has long been functionally considered as the use of energy metabolism. However, our recent study indicated that glycogen metabolism, directed by a cytosolic phosphoenolpyruvate carboxykinase (Pck1), controls the formation and maintenance of CD8+ Tm cells through regulating the redox homeostasis1. This unusual metabolic program raises the question of how Pck1 is upregulated in CD8+ Tm cells. Here, we show that mitochondrial acetyl-CoA is shunted to ketogenesis, which indirectly regulates Pck1 expression. Mechanistically, ketogenesis-derived β-hydroxybutyrate (BHB) is stocked in CD8+ Tm cells, which epigenetically modifies H3K9 of FoxO1 and PGC-1α with β-hydroxybutyrylation so to upregulate these genes expression. As a result, FoxO1 and PGC-1α cooperatively upregulates Pck1 expression, thus directing the carbon flow along the gluconeogenic pathway to glycogen and the pentose phosphate pathway. These results unveil that the ketogenesis acts as an unusual metabolic pathway in CD8+ Tm cells, linking epigenetic modification required for memory development.
2019-04-13 | GSE129723 | GEO
Project description:Fatty acid oxidation and subsequent ketogenesis is one of the major mechanisms to maintain hepatic lipid homeostasis under fasting conditions. Fasting hormone glucagon has been shown to stimulate ketone body production through activation of PPARα; however, the signal pathway linking glucagon to PPARα is largely undiscovered. Here we report that a SIK2-p300-PPARα cascade mediates glucagon's effect on ketogenesis. p300 interacts with PPARα through a conserved LXXLL motif and enhances its transcriptional activity. SIK2 disrupts p300-PPARα interaction by direct phosphorylation of p300 at Ser89, which in turn decreases PPARα-mediated ketogenic gene expression. Moreover, SIK2 phosphorylation defective p300 (p300 S89A) shows increased interaction with PPARα and abolishes suppression of SIK2 on PPARα-mediated ketogenic gene expression in liver. Taken together, our results unveil the signal pathway that mediates fasting induced ketogenesis to maintain hepatic lipid homeostasis.
| S-EPMC4794759 | biostudies-literature
Project description:Short-term starvation (STS or fasting) provides protection to normal cells, mice, and possibly patients from a variety of chemotherapy drugs, but the possibility that it may also protect tumor cells renders its translational potential uncertain. Here we show that fasting cycles can be as effective as toxic chemotherapy drugs, and increase chemotherapy efficacy in the treatment of melanoma, glioma, breast cancer, and neuroblastoma. In vitro, STS sensitizes to chemotherapy 15 of the 17 cancer cell lines tested. In combination with chemotherapy STS results in a synergistic 20-fold increase in DNA damage, increased phosphorylation of pro-aging genes AKT and S6 kinase, reduced expression of stress resistance transcription factors FOXO3a and NFkB, elevated superoxide, and activated caspase-3; all changes not observed in normal tissues. Several of these effects are linked to the activity of heme oxygenase 1 (HO-1), whose modulation was sufficient to regulate chemotherapy-dependent cell death in breast cancer cells. These studies suggest that multiple fasting cycles have the potential to replace certain toxic chemotherapy drugs and to sensitize a wide range of tumors to chemotherapy.
2012-03-21 | GSE28556 | GEO
Project description:we examined if the activation of the anabolic program mediated by the activation of the mTorc1 complex in the fasted state could suppress the robust catabolic programing and enhanced Pparα transcriptional of mice with a liver specific defect in mitochondrial long chain fatty acid oxidation (Cpt2L-/- mice). We found that the activation of mTorc1 in the fasted state was not sufficient to repress Pparα responsive genes or ketogenesis.
2021-06-15 | GSE165701 | GEO