Cardiomyocyte Triglyceride Accumulation and Reduced Ventricular Function in Mice with Obesity Reflect Increased Long Chain Fatty Acid Uptake andDe NovoFatty Acid Synthesis

Abstract

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) anddb/dbandob/obmice. 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. TheVmaxfor saturable fatty acid uptake was increased and significantly correlated with cardiac triglycerides and insulin concentrations.Vmaxalso correlated with expression of genes for the cardiac fatty acid transportersCd36andSlc27a1. Genes forde novofatty 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.