[The effect and pathophysiological mechanism of high free fatty acids(FfAs) on the cardiac structure and function].
OBJECTIVE
To study the pathophysiological links between elevated circulating FFAs concentration and the cardiac structure, and their function in obese insulin resistance rat model.


METHODS
4 weeks age male SD rats were fed with high-fat chow (OB) or standard laboratory chow (NC) respectively. Whole-body insulin sensitivity, the maximum velocity of myocardial contraction (+dp/dt(max)) and the maximum velocity of myocardial diastole (-dp/dt(max)) of intracardiac pressure, and myocardiac cell diameter (MCD) were measured. The concentrations of triglyceride (TG), FFAs and angiotensin II (Ang II) both in blood and in left ventricular portions of heart and the expressions of NF-kappaB, I-kappaB and iNOS in myocardium were analyzed.


RESULTS
OB group developed obesity and left ventricular hypertrophy, and their insulin sensitivity was much lower than that of control group. 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-kappaB and iNOS in myocardium were observed in OB group, while IkappaB lower. Intramyocardial lipid deposition was associated with plasma FFAs concentrations (r = 0.80, P < 0.01). Intramyocardial FFAs concentration was associated with myocardial Ang II concentration (r = 0.74, P < 0.05) and changes in expressions of NF-kappaB (r = 0.86, P < 0.01), iNOS (r = 0.66, P < 0.05). The contractile dysfunction was associated with intramyocardial lipid deposition (r = -0.87, P < 0.01), Ang II (r = -0.52, P < 0.05) and expressions of NF-kappaB (r = -0.57, P < 0. 01), iNOS (r = -0.70, P < 0. 01). The diastolic dysfunction was associated with intramyocardial lipid deposition ( r = -0.85, P < 0.01), Ang II (r = -0.82, P<0.01) and expressions of NF-kappaB (r = -0.75, P < 0.01), iNOS (r = -0.78, P < 0.01).


CONCLUSIONS
In obese/insulin resistance, state ectopic lipid accumulation in myocardium as the results of elevated circulating FFAs and TG concentration impairs cardiac systolic and diastolic functions. It is logical to deduce that ectopic lipid accumulation in myocardium may increase RAS activity and expressions of NF-kappaB, iNOS in myocardium, all of them have important roles to increase the risk of congestive heart failure in obese subjects.
Ke
Liu
L
Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, Chengdu 610041, China.
Yu
Ye-Rong
YR
Zhang
Xuan-E
XE
Zhang
Xiang-Xun
XX
Lu
Zhi-Ming
ZM
D000804:Angiotensin II / Q000097:blood; D000818:Animals; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D020672:I-kappa B Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D014280:Triglycerides / Q000097:blood
D005230:Fatty Acids, Nonesterified; D020672:I-kappa B Proteins; D016328:NF-kappa B; D014280:Triglycerides; D000804:Angiotensin II; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat