YAP: The nexus between metabolism and cardiac remodeling
Chen Gao, Yibin Wang
Chen Gao, Yibin Wang
Published March 15, 2022
Citation Information: J Clin Invest. 2022;132(6):e157664. https://doi.org/10.1172/JCI157664.
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Commentary

YAP: The nexus between metabolism and cardiac remodeling

Abstract

Cardiomyocyte hypertrophy is an integral part of cardiac remodeling that occurs under physiological or pathological stresses. It can lead to heart failure in a pathological form or oppose functional deterioration in a compensatory one. The mechanisms underlying an adaptive outcome of hypertrophy are ill defined. In this issue of the JCI, Kashihara et al. explored the role of the Yes-associated protein 1 (YAP) transcription factor in the heart, using cell culturing and mouse models. YAP activity was found to be associated with changes in genes of the glycolytic and auxiliary pathways under stress. Notably, YAP upregulated glucose transporter 1 (GLUT1), and inhibition of GLUT1 blocked YAP-induced hypertrophy but worsened heart function. These findings suggest that YAP is a regulator of metabolic reprogramming in the heart during compensatory hypertrophy. This insight may help in the development of future therapies for heart failure.

Authors

Chen Gao, Yibin Wang

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Figure 1

Model for YAP-mediated compensatory hypertrophy via metabolic switching.

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Model for YAP-mediated compensatory hypertrophy via metabolic switching....
Cardiac stress, induced by pressure overload, activates YAP to bind the GLUT1 proximal promoter with TEAD1 and HIF-1α. In cardiomyocytes, GLUT1 gene transcription induces glycolysis, shifting cardiomyocytes from fatty acid metabolism. This switch to glycolysis associates with expression changes in the glycolytic, anaplerotic, and auxiliary pathways, resulting in cardiac hypertrophy (2).