High free fatty acids level related with cardiac dysfunction in obese rats

Aim: To determine whether reducing free fatty acids (FFAs) concentration has a protective effect on cardiac structure and function in high-fat-diet-induced obese rat. Methods: Sprague-Dawley rats were randomly divided into normal control, obesity and fenofibrate group. After 8 or 16 weeks, the maximum velocity of myocardial contraction (+dP/dt) and diastole (-dP/dt) were measured. The concentrations of triglyceride, FFAs and angiotensin II were measured. Mitochondrial cytochrome C release and protein levels of NF-kappa B (NF-kappa B) and inducible nitric oxide synthase (iNOS) in myocardium were analyzed. Results: The triglyceride, FFAs and angiotensin II levels were significantly higher in circulating and myocardium in obese rats, associated with lipid deposition, increased mitochondrial cytochrome C release and protein levels of NF-kappa B and iNOS in myocardium. These alterations were reversed by fenofibrate, in parallel with improvement in +dP/dt, -dP/dt and ultrastructures of myocardial mitochondrion. The cardiac dysfunctions had negative correlation with intramyocardial lipid deposition, FFAs, angiotensin II, and protein levels of NF-kappa B and iNOS. Conclusion: Cardiac dysfunction of obese rats could be improved by reducing FFAs level. Intramyocardial lipid accumulation may increase the risk of heart failure in obese rats by increasing renin-angiotensin systems activity and protein levels of NF-kappa B and iNOS in myocardium. (C) 2011 Elsevier Ireland Ltd. All rights reserved.