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.

Intermittent Fasting for Twelve Weeks Leads to Increases in Fat Mass and Hyperinsulinemia in Young Female Wistar Rats

“…Nutrients 2020, 12, 1029; doi:10.3390/nu12041029 www.mdpi.com/journal/nutrients a reduction in blood pressure and heart rate [16][17][18][19][20]; a reduction in inflammation; and protection against neurodegeneration [17][18][19][21][22][23][24][25][26][27][28][29][30].…”

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

“…For example, IF has been reported to influence the circadian clock, intestinal microbiota niche, and to metabolically regulate insulin sensitivity, lipid metabolism, and inflammatory responses which likely contribute to the development of resistance to cardiovascular, neurodegenerative, and metabolic diseases. 9-11…”

A Dynamic Transcriptional Analysis Reveals IL-6 Axis as a Prominent Mediator of Surgical Acute Response in Non-ischemic Mouse Heart

“…Therefore, the sensitivity of the analytical pipeline to detect DETs is highly affected by the statistical power of the study. The experimental design considered a total of 24 animals (eight mice per time point) to meet the statistical parameters which are presented in the section “Materials and Methods.” Surprisingly, in several recent dynamic transcriptomic studies that are involved in ischemia reperfusion (Roy et al, 2006; Kim et al, 2012, 2018; Prat-Vidal et al, 2013; Andreeva et al, 2014; Khan et al, 2017), no power test was carried out to optimize the number of samples, which may have led to the underestimation of the number of DETs. Analytical comparison studies have estimated that a minimum of five and six replicates per condition is required to obtain stable significant results in microarray and RNA sequencing experiments, respectively (Pavlidis et al, 2003; Schurch et al, 2016; Lamarre et al, 2018).…”