The prevalence of type 2 diabetes (T2D) is increasing dramatically in our modern world. Cardiovascular complications are the leading cause of T2D-related morbi-mortality, notably diabetic cardiomyopathy (DCM). This cardiac dysfunction is characterized by hypertrophy and diastolic dysfunction. DCM animal models are required to better define the underlying mechanisms.

We aim to characterize the cardiac and contractile function of the leptin-deficient ob/ob mouse as a potential DCM model.

Twelve weeks-old ob/ob mice were characterized at the metabolic level. Contractile function was evaluated by echocardiography while Ca²⁺ transients were measured by imaging.

Ob/ob mice displayed increased body weight, hyperglycemia and cardiac insulin resistance. Despite a slight thickening of the posterior left ventricular wall, the heart of ob/ob mice does not exhibit any cardiac hypertrophy, further validated by no change in the cardiomyocyte membrane capacitance measured by electrophysiology. Echocardiography revealed no diastolic dysfunction in the ob/ob mice but a mild strain rate reduction with preserved ejection fraction. Peak amplitudes of Ca²⁺ transients were unchanged but time to peak was decreased in the ob/ob cardiomyocyte. Histological analysis showed triglyceride accumulation in the ob/ob heart.

Our data demonstrate that the 12 weeks-old ob/ob mice, well characterized as a T2D and obese mouse model, do not recapitulate the main hallmarks of DCM, i.e. diastolic dysfunction and cardiac hypertrophy. The high accumulation of triglycerides and the subsequent lipotoxicity in the ob/ob cardiomyocytes may rather rely on their obese phenotype than their diabetic one, probably contributing to the early systolic dysfunction.