New research led by the Heather group at the University of Oxford, UK, in collaboration with several EU-METAHEART members, has identified a new metabolic axis underpinning cardiac dysfunction in diabetes.
Abnormal cardiac metabolism is responsible for the development of diabetic cardiomyopathy, identified in up to 70% of people with type 2 diabetes. However, understanding the mechanisms that cause increased cardiac fat metabolism leading to contractile dysfunction have remained elusive.
In a newly published paper in Circ Res, scientists have identified a new metabolic axis, whereby the cardiac fat transport CD36 becomes stuck at the plasma membrane in diabetes due to post-translation S-acylation. The research shows that pharmacologically targeting the enzymes regulating S-acylation can reverse the metabolic dysfunction and restore cardiac function in diabetes. As plasma membrane CD36 is the metabolic gatekeeper influencing all intracellular pathways utilising or regulated by fatty acids, this work paves the way toward the development of new cardiometabolic therapies in diabetes.
Professor Lisa Heather at the University of Oxford, UK comments, ‘Our new metabolic axis explains why the diabetic heart becomes fatty. It also shows that in diabetes fatty acids generate a vicious cycle, propagating greater and greater lipid uptake and lipotoxicity.’
This work was facilitated by the collaborative network generated by COST ACTION EU-METAHEART.
https://www.ahajournals.org/doi/10.1161/CIRCRESAHA.124.325918