Effects of Pioglitazone on High-Fat-Diet–Induced Ventricular Remodeling and Dysfunction in Rats

Abstract

Objective: To investigate the effect of pioglitazone on high-fat (HF)-diet–induced left ventricular (LV) hypertrophy and dysfunction in rats. Methods: A total of 36 male Sprague-Dawley rats were randomly divided into 3 groups, namely, control, HF diet, and pioglitazone treatment group. High-fat diet group (HF group) animals were treated with HF diet for 30 weeks, whereas pioglitazone group was treated with HF diet for 30 weeks and pioglitazone in the last 6 weeks of the 30-week treatment. Fasting plasma free fatty acids (FFAs), serum, and myocardial triglyceride were measured. Left ventricular function was assessed by echocardiography. Renin, angiotensin II, and angiotensin types 1 and 2 (AT1/AT2) receptors in the myocardium were analyzed by immunohistochemistry and real-time polymerase chain reaction (PCR). Results: Systolic blood pressure, plasma FFA, serum, and myocardial triglyceride concentrations in HF group were higher than in control and pioglitazone groups ( P < .01). There was no significant difference in LV weight index and LV posterior wall thickness between HF and pioglitazone groups; both were higher than in the control group ( P < .01). Left ventricular ejection fraction, fraction of shortening, and cardiac index in HF group were lower than in the control and pioglitazone groups ( P < .05). Myocardial expression of angiotensin II and AT1 receptor protein in HF group was higher when compared with the control and pioglitazone groups ( P < .01). Myocardial renin and angiotensin II messenger RNA (mRNA) in HF group was also higher when compared with the control and pioglitazone groups, whereas the expression of AT2 mRNA was lower ( P < .01). Conclusion: Pioglitazone diminished HF-diet–induced LV dysfunction. These effects may be related to a reduction in blood pressure, myocardial triglycerides sedimentary, and suppression of renin–angiotensin system.