Ablating the Rab-GTPase Activating Protein TBC1D1 Predisposes Rats to High Fat Diet-Induced Cardiomyopathy

Although the role of TBC1D1 within the heart remains unknown, expression of TBC1D1 increases in the left ventricle following an acute infarction, suggesting a biological importance within this tissue. We investigated the mechanistic role of TBC1D1 within the heart, aiming to establish the consequences of attenuating TBC1D1 signalling in the development of diabetic cardiomyopathy, as well as to determine potential sex differences. TBC1D1 ablation increased plasma membrane fatty acid binding protein content and myocardial palmitate oxidation. Following high‐fat feeding, TBC1D1 ablation dramatically increased fibrosis and induced end‐diastolic dysfunction in both male and female rats in the absence of changes in mitochondrial bioenergetics. Altogether, independent of sex, ablating TBC1D1 predisposes the left ventricle to pathological remodelling following high‐fat feeding, and suggests TBC1D1 protects against diabetic cardiomyopathy.