GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure

Renata O Pereira; Adam R Wende; Curtis Olsen; Jamie Soto; Tenley Rawlings; Yi Zhu; Christian Riehle; E. Dale Abel

doi:10.1016/j.yjmcc.2014.02.011

Back

GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure

Journal article

Peer reviewed

GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure

Renata O Pereira, Adam R Wende, Curtis Olsen, Jamie Soto, Tenley Rawlings, Yi Zhu, Christian Riehle and E. Dale Abel

Journal of molecular and cellular cardiology, Vol.72, pp.95-103

07/2014

DOI: 10.1016/j.yjmcc.2014.02.011

PMCID: PMC4037364

PMID: 24583251

View Online

Abstract

The aim of this study was to determine whether endogenous GLUT1 induction and the increased glucose utilization that accompanies pressure overload hypertrophy (POH) are required to maintain cardiac function during hemodynamic stress, and to test the hypothesis that lack of GLUT1 will accelerate the transition to heart failure. To determine the contribution of endogenous GLUT1 to the cardiac adaptation to POH, male mice with cardiomyocyte-restricted deletion of the GLUT1 gene (G1KO) and their littermate controls (Cont) were subjected to transverse aortic constriction (TAC). GLUT1 deficiency reduced glycolysis and glucose oxidation by 50%, which was associated with a reciprocal increase in fatty acid oxidation (FAO) relative to controls. Four weeks after TAC, glycolysis increased and FAO decreased by 50% in controls, but were unchanged in G1KO hearts relative to shams. G1KO and controls exhibited equivalent degrees of cardiac hypertrophy, fibrosis, and capillary density loss after TAC. Following TAC, in vivo left ventricular developed pressure was decreased in G1KO hearts relative to controls, but+dP/dt was equivalently reduced in Cont and G1KO mice. Mitochondrial function was equivalently impaired following TAC in both Cont and G1KO hearts. GLUT1 deficiency in cardiomyocytes alters myocardial substrate utilization, but does not substantially exacerbate pressure-overload induced contractile dysfunction or accelerate the progression to heart failure. •Endogenous GLUT1 is dispensable for normal cardiac function•Lack of GLUT1 impairs metabolic flexibility following transverse aortic constriction.•GLUT1 deficiency does not accelerate the transition to heart failure in POH.•GLUT1 is not critical for the initial adaptation to POH.

Cardiac hypertrophy

Glucose transport

Cardiac metabolism

Details

Title: Subtitle: GLUT1 deficiency in cardiomyocytes does not accelerate the transition from compensated hypertrophy to heart failure
Creators: Renata O Pereira - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Adam R Wende - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Curtis Olsen - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Jamie Soto - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Tenley Rawlings - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Yi Zhu - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Christian Riehle - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
E. Dale Abel - Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, UT, 84112, USA
Resource Type: Journal article
Publication Details: Journal of molecular and cellular cardiology, Vol.72, pp.95-103
DOI: 10.1016/j.yjmcc.2014.02.011
PMID: 24583251
PMCID: PMC4037364
NLM abbreviation: J Mol Cell Cardiol
ISSN: 0022-2828
eISSN: 1095-8584
Publisher: Elsevier Ltd
Language: English
Date published: 07/2014
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
Record Identifier: 9984024534402771

Metrics

18 Record Views

41 Times Cited - Web of Science