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Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice

ABSTRACT: Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice

PROVIDER: PRJNA1174773 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR31040104_1.fastq.gz	Fastqsanger.gz
	SRR31040104_2.fastq.gz	Fastqsanger.gz
	SRR31040105_1.fastq.gz	Fastqsanger.gz
	SRR31040105_2.fastq.gz	Fastqsanger.gz
	SRR31040106_1.fastq.gz	Fastqsanger.gz

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Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice

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

Fasting-mimicking Diet in Patients Undergoing Active Cancer Treatment

Project description:This is a pilot, single arm prospective trial assessing feasibility, safety and effects on patient nutritional status of a 5-day fasting-mimicking diet (FMD) in patients with different cancer types and concomitant anticancer treatment.

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Fasting-mimicking diet reshapes antitumor immunity in cancer patients

Project description:To investigate whether the fasting-mimicking diet (FMD) affects intratumor immunity, we assessed the impact of one FMD cycle before surgery in matched tumor tissue specimens from 22 early-stage breast cancer patients. At the tumor level, FMD activated antitumor immune programs in early-stage breast cancer patients.

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Adipocyte p53 coordinates the adipose tissue immune cell landscape upon intermittent fasting

Project description:In obesity, sustained adipose tissue (AT) inflammation constitutes a cellular memory that limits the effectiveness of weight loss interventions. Yet, its fasting regimen-dependent regulation is unknown. Here, we show that cyclic intermittent fasting (IF) exacerbates the lipid-associated macrophage (LAM) inflammatory phenotype of visceral AT in obese mice. Importantly, we provide evidence that this increase in LAM abundance is almost entirely dependent on p53-driven adipocyte apoptosis. Adipocyte-specific deletion of p53 prevents LAM accumulation in AT during IF and increases the catabolic state of adipocytes, ameliorates metabolic flexibility, and insulin sensitivity. Finally, in cohorts of obese/diabetic patients, we describe a p53 polymorphism that links to long-term efficacy of a fasting-mimicking diet and that the expression of LAM markers and p53 in AT negatively correlates with maintaining weight loss after bariatric surgery. Overall, our results demonstrate that p53 signaling in adipocytes dictates LAM accumulation in AT under IF and that adipocyte p53 modulates fasting effectiveness in mice and humans.

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Transcriptome analysis of mouse heart under different intermittent fasting conditions

Project description:Various intermittent fasting regimes are popularly being practiced but the scientific understanding for the mechanisms of intermittent fasting remains unclear. Observing the overall transcriptomic changes in specific organs, including heart, may contribute substantially in understanding the diverse effects of intermittent fasting. Our current study further investigate the differential transcriptomic changes in the heart among the different regimes of intermittent fasting as well.

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Fasting-mimicking diet synergizes with ferroptosis against quiescent, chemotherapy-resistant cells

Project description:Fasting-mimicking diet synergizes with ferroptosis against quiescent, chemotherapy-resistant cells

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Adipocyte p53 coordinates the adipose tissue immune cell landscape upon intermittent fasting

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Intermittent fasting alters the spatiotemporal atlas of transcriptomes

Project description:Transcription factors may orchestrate the health benefits of intermittent fasting through directing the expression of genome. Here, we find intermittent fasting can spin the spatiotemporal profile of transcription factors, and provide an atlas of transcription factors in biological space, time and feeding regimen.

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Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke

Project description:Intermittent fasting is previously reported to exhibit neuroprotection against experimental ischemic stroke. However, the detailed understanding of protection mechanisms are lacking. By observing the overall transcriptomic changes in each timepoint of ischemic stroke would benefit the understanding of underlying active pathways and mechanisms. Here, we conduct experimental MCAO ischemic stroke on mice exposed to different daily intermittent fasting method to compare not only among the ischemic stroke timepoints but also the efficacy of different intermittent fasting interventions. Our current study presented the transcriptomic changes for the first time in specific timepoints of ischemic stroke as well as under the condition of intermittent fasting. A number of neuroprotective mechanisms-related genes were significantly affected by intermittent fasting conditions in differential manners.

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