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Publication : Metabolic reprogramming of murine cardiomyocytes during autophagy requires the extracellular nutrient sensor decorin.

First Author  Gubbiotti MA Year  2018
Journal  J Biol Chem Volume  293
Issue  43 Pages  16940-16950
PubMed ID  30049794 Mgi Jnum  J:272810
Mgi Id  MGI:6268555 Doi  10.1074/jbc.RA118.004563
Citation  Gubbiotti MA, et al. (2018) Metabolic reprogramming of murine cardiomyocytes during autophagy requires the extracellular nutrient sensor decorin. J Biol Chem 293(43):16940-16950
abstractText  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-beta-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.
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