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

OBJECTIVE

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-κB) 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-κB 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-κB and iNOS.

CONCLUSIONS

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-κB and iNOS in myocardium.