RRC ID 66053
Author Tanegashima K, Sato-Miyata Y, Funakoshi M, Nishito Y, Aigaki T, Hara T.
Title Epigenetic regulation of the glucose transporter gene Slc2a1 by β-hydroxybutyrate underlies preferential glucose supply to the brain of fasted mice.
Journal Genes Cells
Abstract We carried out liquid chromatography-tandem mass spectrometry analysis of metabolites in mice. Those metabolome data showed that hepatic glucose content is reduced, but that brain glucose content is unaffected, during fasting, consistent with the priority given to brain glucose consumption during fasting. The molecular mechanisms for this preferential glucose supply to the brain are not fully understood. We also showed that the fasting-induced production of the ketone body β-hydroxybutyrate (β-OHB) enhances expression of the glucose transporter gene Slc2a1 (Glut1) via histone modification. Upon β-OHB treatment, Slc2a1 expression was up-regulated, with a concomitant increase in H3K9 acetylation at the critical cis-regulatory region of the Slc2a1 gene in brain microvascular endothelial cells and NB2a neuronal cells, shown by quantitative PCR analysis and chromatin immunoprecipitation assay. CRISPR/Cas9-mediated disruption of the Hdac2 gene increased Slc2a1 expression, suggesting that it is one of the responsible histone deacetylases (HDACs). These results confirm that β-OHB is a HDAC inhibitor and show that β-OHB plays an important role in fasting-induced epigenetic activation of a glucose transporter gene in the brain.
Volume 22(1)
Pages 71-83
Published 2017-1-1
DOI 10.1111/gtc.12456
PMID 27935189
MeSH 3-Hydroxybutyric Acid / metabolism Acetylation Animals Brain / metabolism Brain / pathology CRISPR-Cas Systems Endothelial Cells / metabolism Epigenesis, Genetic / genetics* Fasting Glucose / metabolism* Glucose Transporter Type 1 / biosynthesis* Glucose Transporter Type 1 / metabolism Histone Code / genetics Histone Deacetylase 2 / genetics Histone Deacetylase 2 / metabolism* Ketone Bodies / metabolism Metabolome / genetics Mice Neurons / metabolism
IF 1.655
Human and Animal Cells NB2a(RCB2639)