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

Joonki Kim, Sung Wook Kang, Karthik Mallilankaraman, Sang Ha Baik, James C. Lim, Priyanka Balaganapathy, David T. She, Ker Zhing Lok, David Y. Fann, Uma Thambiayah, Sung Chun Tang, Alexis Michelle Stranahan, S. Thameem Dheen, Mathias Gelderblom, Raymond C. Seet, Vardan T. Karamyan, Raghu Vemuganti, Christopher G. Sobey, Mark P. Mattson, Dong Gyu JoThiruma V. Arumugam

Research output: Contribution to journalArticle

6 Citations (Scopus)

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. Midcoronal 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.

Original languageEnglish (US)
Pages (from-to)1497-1513
Number of pages17
JournalHuman Molecular Genetics
Volume27
Issue number9
DOIs
StatePublished - May 1 2018

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Gene Expression Profiling
Fasting
Stroke
Transcriptome
Reperfusion
Up-Regulation
RNA Sequence Analysis
Neuronal Plasticity
Middle Cerebral Artery Infarction
Brain
Neurodegenerative Diseases
Brain Injuries
Energy Metabolism
Molecular Biology
Down-Regulation
Ischemia
Genome
Diet
Messenger RNA
Research

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Kim, J., Kang, S. W., Mallilankaraman, K., Baik, S. H., Lim, J. C., Balaganapathy, P., ... Arumugam, T. V. (2018). Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke. Human Molecular Genetics, 27(9), 1497-1513. https://doi.org/10.1093/hmg/ddy057

Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke. / Kim, Joonki; Kang, Sung Wook; Mallilankaraman, Karthik; Baik, Sang Ha; Lim, James C.; Balaganapathy, Priyanka; She, David T.; Lok, Ker Zhing; Fann, David Y.; Thambiayah, Uma; Tang, Sung Chun; Stranahan, Alexis Michelle; Dheen, S. Thameem; Gelderblom, Mathias; Seet, Raymond C.; Karamyan, Vardan T.; Vemuganti, Raghu; Sobey, Christopher G.; Mattson, Mark P.; Jo, Dong Gyu; Arumugam, Thiruma V.

In: Human Molecular Genetics, Vol. 27, No. 9, 01.05.2018, p. 1497-1513.

Research output: Contribution to journalArticle

Kim, J, Kang, SW, Mallilankaraman, K, Baik, SH, Lim, JC, Balaganapathy, P, She, DT, Lok, KZ, Fann, DY, Thambiayah, U, Tang, SC, Stranahan, AM, Dheen, ST, Gelderblom, M, Seet, RC, Karamyan, VT, Vemuganti, R, Sobey, CG, Mattson, MP, Jo, DG & Arumugam, TV 2018, 'Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke', Human Molecular Genetics, vol. 27, no. 9, pp. 1497-1513. https://doi.org/10.1093/hmg/ddy057
Kim J, Kang SW, Mallilankaraman K, Baik SH, Lim JC, Balaganapathy P et al. Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke. Human Molecular Genetics. 2018 May 1;27(9):1497-1513. https://doi.org/10.1093/hmg/ddy057
Kim, Joonki ; Kang, Sung Wook ; Mallilankaraman, Karthik ; Baik, Sang Ha ; Lim, James C. ; Balaganapathy, Priyanka ; She, David T. ; Lok, Ker Zhing ; Fann, David Y. ; Thambiayah, Uma ; Tang, Sung Chun ; Stranahan, Alexis Michelle ; Dheen, S. Thameem ; Gelderblom, Mathias ; Seet, Raymond C. ; Karamyan, Vardan T. ; Vemuganti, Raghu ; Sobey, Christopher G. ; Mattson, Mark P. ; Jo, Dong Gyu ; Arumugam, Thiruma V. / Transcriptome analysis reveals intermittent fasting-induced genetic changes in ischemic stroke. In: Human Molecular Genetics. 2018 ; Vol. 27, No. 9. pp. 1497-1513.
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