Metabo-epigenetic regulatory circuits of heart disease caused by inherited and acquired lipid accumulation (A01)

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Inherited neutral lipid storage disease with cardiomyopathy (NLSD-CM) is caused by mutations in PNPLA2, encoding a lipid droplet (LD)-associated protein, and is characterized by massive lipid accumulation. Using mouse models of genetic and acquired NLSD-CM, we have demonstrated the involvement of histone deacetylases (HDACs) in the development of diastolic dysfunction. The aim of the project is to elucidate the molecular mechanisms by which HDACs regulate lipid metabolism and cardiac function, to unravel the metabo-epigenetic circuits connecting chromatin state with metabolic and lysosomal-autophagic control in NLSD-CM.