The Effect Of Free Fatty Acids On The Cardiac Structure And Function Of Obese Rats

Objective Obesity is often associated with cardiac hypertrophy and abnormal cardiac function, the mechanism of which is still not quite clear.Elevated circulating free fatty acids may play an important part in the development of heart dysfunction.This study is designde to explore the changes of cardiac structure and function of obese rats after circulating free fatty acids concentration being reduced by fmofibrate or insulin.Materials and methods Male S-D rats, 4 weeks in age, were devided into four groups randomly: normal control group(NC group),obesity group (OB group) ,obesity plus fenofibrate group(OB+F group)and obesity plus inslin group(OB+I group). The NC group rats were fed with normal chow, and the others fed with high fat chow. Four weeks later, fenofibrate was given to the OB+F group rats , and OB+I group rats were injected with insulin. Eight and sixteen weeks later, the maximum velocity of myocardial contraction (+dP/dt max) and the maximum velocity of myocardial diastole (-dP/dt max) of intracardiac pressure were measured by physiological polygraph to evaluate cardiac function. The concentrations of triglyceride (TG), FFAs and angiotensin II (Ang II) both in blood and in left ventricular portions of heart were measured. The ultrastructures of myocardiac cells were observed by electron microscope. The expressions of NF-κB and iNOS in myocardium were analyzed by the methods of immunohistochemistry.Results The OB group rats developed obesity and left ventricular hypertrophy. Obese rats had higher plasma concentrations of TG, FFAs and Ang II. Accordingly, dramatic lipid deposition occurred within cardiomyocytes of obese rats, and the value of myocardiac Ang II was also increased. High-fat diet also induced a progressive decrease in values of +dP/dt max and -dP/dt max. The higher expressions of NF-κB and iNOS in myocardium were observed in OB group. The concentration of myocardial endochylema cytochrome C was higher, meanwhile, the value of mitochondrial cytochrome C is lower. Histological examinations showed marked alterations within myocardial mitochondrion in obese rats. Being treated with fenofibrate, the concentrations of plasma TG and FFAs of obese rats were reduced. Accordingly, intramyocardial lipid deposition was download.And the contractile and diastolic function of obese rats were improved. The expressions of iNOS and NF-κB and the concentrations of AngII and cytochrome C within myocardium were also decreased. And the changes of mitochondrial structure were diminished, too. Intramyocardial lipid deposition was associated with plasma TG and FFAs concentrations. Intramyocardial lipid overload in the hearts was associated with myocardial Ang II concentration and changes in expressions of NF-κB, iNOS. The contractile and diastolic dysfunctions had negative correlation with intramyocardial lipid deposition, Ang II, endochylema cytochrome C, and expressions of NF-κB, iNOS.Conclusion Cardiac hypertrophy and dysfunction of obese rats could be improved by reducing the concentration of free fatty acids in the circulation and myocardium. Ectopic lipid accumulation in myocardium may increase the risk of heart failure in obese subjects by increasing RAS activity and expressions of NF-κB, iNOS in myocardium.