Obesity in mice significantly reduced ejection fraction and fractional shortening, accompanied by increased saturable fatty acid uptake and upregulated de novo fatty acid synthesis genes.
Obesity in mouse models leads to reduced ventricular function associated with increased fatty acid uptake, de novo synthesis, and downregulated oxidative phosphorylation genes.
A nonarteriosclerotic cardiomyopathy is increasingly seen in obese patients. Seeking a rodent model, we studied cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression in male C57BL/6J control mice and three obesity groups: similar mice fed a high-fat diet (HFD) and db/db and ob/ob mice. At sacrifice, all obesity groups had increased body and heart weights and fatty livers. By echocardiography, ejection fraction (EF) and fractional shortening (FS) of left ventricular diameter during systole were significantly reduced. The V(max) for saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations. V(max) also correlated with expression of genes for the cardiac fatty acid transporters Cd36 and Slc27a1. Genes for de novo fatty acid synthesis (Fasn, Scd1) were also upregulated. Ten oxidative phosphorylation pathway genes were downregulated, suggesting that a decrease in cardiomyocyte ATP synthesis might explain the decreased contractile function in obese hearts.
Ge et al. (Wed,) conducted a other in Obesity-related cardiomyopathy. Obesity models (HFD, db/db, ob/ob) vs. Control mice was evaluated on Cardiac histology, function, cardiomyocyte fatty acid uptake, and transporter gene expression. Obesity in mice significantly reduced ejection fraction and fractional shortening, accompanied by increased saturable fatty acid uptake and upregulated de novo fatty acid synthesis genes.