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

ABSTRACT: Genetic changes due to dietary intervention in the form of either calorie restriction (CR) or intermittent fasting (IF) are not reported in detail until now. However, it is well established that both CR and IF extend the lifespan and protect against neurodegenerative diseases and stroke. The current research aims were first to describe the transcriptomic changes in brains of IF mice and, second, to determine whether IF induces extensive transcriptomic changes following ischemic stroke to protect the brain from injury. Mice were randomly assigned to ad libitum feeding (AL), 12 (IF12) or 16 (IF16) h daily fasting. Each diet group was then subjected to sham surgery or middle cerebral artery occlusion and consecutive reperfusion. Mid-coronal sections of ipsilateral cerebral tissue were harvested at the end of the 1 h ischemic period or at 3, 12, 24 or 72 h of reperfusion, and genome-wide mRNA expression was quantified by RNA sequencing. The cerebral transcriptome of mice in AL group exhibited robust, sustained up-regulation of detrimental genetic pathways under ischemic stroke, but activation of these pathways was suppressed in IF16 group. Interestingly, the cerebral transcriptome of AL mice was largely unchanged during the 1 h of ischemia, whereas mice in IF16 group exhibited extensive up-regulation of genetic pathways involved in neuroplasticity and down-regulation of protein synthesis. Our data provide a genetic molecular framework for understanding how IF protects brain cells against damage caused by ischemic stroke, and reveal cellular signaling and bioenergetic pathways to target in the development of clinical interventions.

SUBMITTER: Kim J

PROVIDER: S-EPMC5915958 | biostudies-literature |

REPOSITORIES: biostudies-literature

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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.

2018-07-11 | GSE116878 | GEO

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

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

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Genome-Wide Transcriptome Analysis Reveals Intermittent Fasting-Induced Metabolic Rewiring in the Liver.

Project description:Scope: Intermittent fasting (IF) has been extensively reported to promote improved energy homeostasis and metabolic switching. While IF may be a plausible strategy to ameliorate the epidemiological burden of disease in many societies, our understanding of the underlying molecular mechanisms behind such effects is still lacking. The present study has sought to investigate the relationship between IF and changes in gene expression. We focused on the liver, which is highly sensitive to metabolic changes due to energy status. Mice were randomly assigned to ad libitum feeding or IF for 16 hours per day or for 24 hours on alternate days for 3 months, after which genome-wide transcriptome analysis of the liver was performed using RNA sequencing. Our findings revealed that IF caused robust transcriptomic changes in the liver that led to a complex array of metabolic changes. We also observed that the IF regimen produced distinct profiles of transcriptomic changes, highlighting the significance of temporally different periods of energy restriction. Our results suggest that IF can regulate metabolism via transcriptomic mechanisms and provide insight into how genetic interactions within the liver might lead to the numerous metabolic benefits of IF.

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Genome-Wide Transcriptome Analysis Reveals Intermittent Fasting-Induced Metabolic Rewiring in the Liver

Project description:Intermittent fasting (IF) has been extensively reported to participate in improved energy homeostasis and metabolic switching, which in turn promotes protection against numerous age-associated metabolic diseases that have plagued the global population in recent years. Despite the observation that IF may be a plausible strategy to ameliorate these epidemiological burdens in many societies, investigation into the underlying molecular mechanisms behind these purported effects are still in their infancy. Particularly, the relationship between IF and genetic changes are poorly understood, which forms the basis of this research.

2019-07-31 | GSE130127 | GEO

Sequential Transcriptome Changes in the Penumbra after Ischemic Stroke.

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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.

2023-09-27 | GSE133290 | GEO

Proteomic Analysis of Human Plasma during Intermittent Fasting.

Project description:Intermittent fasting (IF) increases lifespan and decreases metabolic disease phenotypes and cancer risk in model organisms, but the health benefits of IF in humans are less clear. Human plasma derived from clinical trials is one of the most difficult sample sets to analyze using mass spectrometry-based proteomics due to the extensive sample preparation required and the need to process many samples to achieve statistical significance. Here, we describe an optimized and accessible device (Spin96) to accommodate up to 96 StageTips, a widely used sample preparation medium enabling efficient and consistent processing of samples prior to LC-MS/MS. We have applied this device to the analysis of human plasma from a clinical trial of IF. In this longitudinal study employing 8-weeks IF, we identified significant abundance differences induced by the IF intervention, including increased apolipoprotein A4 (APOA4) and decreased apolipoprotein C2 (APOC2) and C3 (APOC3). These changes correlated with a significant decrease in plasma triglycerides after the IF intervention. Given that these proteins have a role in regulating apolipoprotein particle metabolism, we propose that IF had a positive effect on lipid metabolism through modulation of HDL particle size and function. In addition, we applied a novel human protein variant database to detect common protein variants across the participants. We show that consistent detection of clinically relevant peptides derived from both alleles of many proteins is possible, including some that are associated with human metabolic phenotypes. Together, these findings illustrate the power of accessible workflows for proteomics analysis of clinical samples to yield significant biological insight.

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