Cardiac ablation of ALCAT1 in a mouse model restored tetralinoleoyl cardiolipin content and mitochondrial function, mitigating diabetic cardiomyopathy by promoting fatty acid oxidation.
Does cardiac ablation of ALCAT1 mitigate diabetic cardiomyopathy in a mouse model?
ALCAT1 is identified as a central mediator of diabetic cardiomyopathy, and its ablation restores mitochondrial integrity and mitigates the disease in a mouse model.
Cardiolipin (CL) is a mitochondria-specific phospholipid essential for maintaining cardiac bioenergetic function. In diabetes, the depletion of tetralinoleoyl cardiolipin (TLCL)-the predominant CL species in healthy myocardium-has been implicated in the pathogenesis of diabetic cardiomyopathy (DCM). However, the mechanisms underlying TLCL loss remain poorly understood. ALCAT1, an acyltransferase that mediates pathological remodeling of CL under oxidative stress, has been proposed as a key factor in this process. Using a cardiac-specific ALCAT1 knockout mouse model, we demonstrate a causal role of ALCAT1 in the onset and progression of DCM. We show that hyperglycemia-induced upregulation of ALCAT1 leads to TLCL depletion, mitochondrial dysfunction, and lipotoxicity in the heart. Remarkably, cardiac ablation of ALCAT1 not only restored TLCL content and mitochondrial function but also mitigated DCM by promoting fatty acid oxidation in the heart. Together, these findings identify ALCAT1 as a central mediator of diabetic cardiomyopathy through its disruption of fatty acid oxidation and mitochondrial integrity.
Jia et al. (Fri,) conducted a other in Diabetic cardiomyopathy. Cardiac ablation of ALCAT1 was evaluated on TLCL content, mitochondrial function, and DCM progression. Cardiac ablation of ALCAT1 in a mouse model restored tetralinoleoyl cardiolipin content and mitochondrial function, mitigating diabetic cardiomyopathy by promoting fatty acid oxidation.