RT Journal Article SR Electronic T1 Glucose metabolism promotes neonatal heart regeneration JF bioRxiv FD Cold Spring Harbor Laboratory SP 865790 DO 10.1101/865790 A1 Viviana M Fajardo Martinez A1 Iris Feng A1 Bao Ying Chen A1 Cesar A Perez A1 Baochen Shi A1 Peter Clark A1 Rong Tian A1 Ching-Ling Lien A1 Matteo Pellegrini A1 Heather Christofk A1 Haruko Nakano A1 Atsushi Nakano YR 2019 UL http://biorxiv.org/content/early/2019/12/09/865790.abstract AB The mammalian heart switches its main metabolic substrate from glucose to fatty acids shortly after birth. This metabolic switch coincides with the loss of regenerative capacity in the heart. However, it is unknown whether glucose metabolism itself regulates heart regeneration. Here, we report that glucose metabolism is a determinant of regenerative capacity in the neonatal mammalian heart. Cardiac-specific overexpression of Glut1, the embryonic form of constitutively active glucose transporter, resulted in an increase in glucose uptake and concomitant glycogen storage in postnatal heart. Upon cryoinjury, Glut1 transgenic hearts showed higher regenerative capacity with less fibrosis than non-transgenic control hearts. Interestingly, flow cytometry analysis revealed two distinct populations of ventricular cardiomyocytes: Tnnt2-high and Tnnt2-low cardiomyocytes, the latter of which showed significantly higher mitotic activity in response to high intracellular glucose in Glut1 transgenic hearts. Metabolic profiling shows that Glut1-transgenic hearts have a significant increase in the glucose metabolites upon injury, and inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level. Our data suggest that the increased in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.