Alterations in lipid metabolism within the heart may have a causal role in the establishment of
diabetic cardiomyopathy; however, this remains equivocal. Therefore, in the current study we determined cardiac mitochondrial bioenergetics in ZDF rats before overt
type 2 diabetes and
diabetic cardiomyopathy developed. In addition, we utilized
resveratrol, a compound previously shown to improve, prevent or reverse cardiac dysfunction in high-fat-fed rodents, as a tool to potentially recover dysfunctions within mitochondria. Fasting
blood glucose and invasive left ventricular haemodynamic analysis confirmed the absence of
type 2 diabetes and
diabetic cardiomyopathy. However,
fibrosis was already increased (P < 0.05) ∼70% in ZDF rats at this early stage in
disease progression. Assessments of mitochondrial
ADP and
pyruvate respiratory kinetics in permeabilized fibres from the left ventricle revealed normal electron transport chain function and content. In contrast, the apparent Km to
palmitoyl-CoA (P-
CoA) was increased (P < 0.05) ∼60%, which was associated with an accumulation of intracellular triacylgycerol,
diacylglycerol and
ceramide species. In addition, the capacity for mitochondrial
reactive oxygen species emission was increased (P < 0.05) ∼3-fold in ZDF rats. The provision of
resveratrol reduced
fibrosis, P-
CoA respiratory sensitivity, reactive
lipid accumulation and mitochondrial
reactive oxygen species emission rates. Altogether the current data support the supposition that a chronic dysfunction within mitochondrial
lipid-supported bioenergetics contributes to the development of
diabetic cardiomyopathy, as this was present before overt diabetes or cardiac dysfunction. In addition, we show that
resveratrol supplementation prevents these changes, supporting the belief that
resveratrol is a potent therapeutic approach for preventing
diabetic cardiomyopathy.