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This research was originally published in Journal of Biological Chemistry. Gubbiotti, M. A., Seifert, E., Rodeck, U., Hoek, J. B., & Iozzo, R. V.. Metabolic reprogramming of murine cardiomyocytes during autophagy requires the extracellular nutrient sensor decorin. Journal of Biological Chemistry. 2018; 293(43):16940-16950. © the American Society for Biochemistry and Molecular Biology.


The extracellular matrix is a master regulator of tissue homeostasis in health and disease. Here we examined how the small, leucine-rich, extracellular matrix proteoglycan decorin regulates cardiomyocyte metabolism during fasting in vivo. First, we validated in Dcn-/- mice that decorin plays an essential role in autophagy induced by fasting. High-Throughput metabolomics analyses of cardiac tissue in Dcn-/- mice subjected to fasting revealed striking differences in the hexosamine biosynthetic pathway resulting in aberrant cardiac O-β-N-Acetylglycosylation as compared with WT mice. Functionally, Dcn-/- mice maintained cardiac function at a level comparable with nonfasted animals whereas fasted WT mice showed reduced ejection fraction. Collectively, our results suggest that reduced sensing of nutrient deprivation in the absence of decorin preempts functional adjustments of cardiac output associated with metabolic reprogramming. © 2018 Gubbiotti et al.

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