FoxO1-zDHHC4-CD36 S-Acylation Axis Drives Metabolic Dysfunction in Diabetes.

Background: The fatty acid (FA) transporter CD36 (FA translocase/cluster of differentiation 36) is the gatekeeper of cardiac FA metabolism. Preferential localisation of CD36 to the sarcolemma is one of the initiating cellular responses in the development of muscle insulin resistance and in the type 2 diabetic heart. Post-translational S-acylation controls protein trafficking, and in this study we hypothesised that increased CD36 S-acylation may underpin the preferential sarcolemmal localisation of CD36, driving metabolic and contractile dysfunction in diabetes.

AICAR confers prophylactic cardioprotection in doxorubicin-induced heart failure in rats.

Doxorubicin (DOX) is a widely used chemotherapeutic agent that can cause serious cardiotoxic side effects, leading to heart failure (HF). Impaired mitochondrial function is thought to be key factor driving progression into HF. We have previously shown in a rat model of DOX-HF that heart failure with reduced ejection fraction correlates with mitochondrial loss and dysfunction.