GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration

Abstract 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 regulates heart regeneration. Here, we report tha...

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Autores principales:	Viviana M. Fajardo, Iris Feng, Bao Ying Chen, Cesar A. Perez-Ramirez, Baochen Shi, Peter Clark, Rong Tian, Ching-Ling Lien, Matteo Pellegrini, Heather Christofk, Haruko Nakano, Atsushi Nakano
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/35f4d047b40e4f74bc40708dc8bfcb3a
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spelling	oai:doaj.org-article:35f4d047b40e4f74bc40708dc8bfcb3a2021-12-02T17:32:58ZGLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration10.1038/s41598-021-88159-x2045-2322https://doaj.org/article/35f4d047b40e4f74bc40708dc8bfcb3a2021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88159-xhttps://doaj.org/toc/2045-2322Abstract 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 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 accumulation of 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 including nucleotides upon injury. Inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level, suggesting that the glucose enhances the cardiomyocyte regeneration through the supply of nucleotides. Our data suggest that the increase in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.Viviana M. FajardoIris FengBao Ying ChenCesar A. Perez-RamirezBaochen ShiPeter ClarkRong TianChing-Ling LienMatteo PellegriniHeather ChristofkHaruko NakanoAtsushi NakanoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Viviana M. Fajardo Iris Feng Bao Ying Chen Cesar A. Perez-Ramirez Baochen Shi Peter Clark Rong Tian Ching-Ling Lien Matteo Pellegrini Heather Christofk Haruko Nakano Atsushi Nakano GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
description	Abstract 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 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 accumulation of 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 including nucleotides upon injury. Inhibition of the nucleotide biosynthesis abrogated the regenerative advantage of high intra-cardiomyocyte glucose level, suggesting that the glucose enhances the cardiomyocyte regeneration through the supply of nucleotides. Our data suggest that the increase in glucose metabolism promotes cardiac regeneration in neonatal mouse heart.
format	article
author	Viviana M. Fajardo Iris Feng Bao Ying Chen Cesar A. Perez-Ramirez Baochen Shi Peter Clark Rong Tian Ching-Ling Lien Matteo Pellegrini Heather Christofk Haruko Nakano Atsushi Nakano
author_facet	Viviana M. Fajardo Iris Feng Bao Ying Chen Cesar A. Perez-Ramirez Baochen Shi Peter Clark Rong Tian Ching-Ling Lien Matteo Pellegrini Heather Christofk Haruko Nakano Atsushi Nakano
author_sort	Viviana M. Fajardo
title	GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
title_short	GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
title_full	GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
title_fullStr	GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
title_full_unstemmed	GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
title_sort	glut1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/35f4d047b40e4f74bc40708dc8bfcb3a
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GLUT1 overexpression enhances glucose metabolism and promotes neonatal heart regeneration

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