Xiaodong Sun1, Hua Pan, Huiwen Tan, Yerong Yu. 1. Department of Endocrinology and Metabolism, West China Hospital, Sichuan University, No. 37, Guoxue Road, Chengdu 610041, Sichuan, China.
Abstract
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-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. 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-κB and iNOS in myocardium.
AIM: To determine whether reducing free fatty acids (FFAs) concentration has a protective effect on cardiac structure and function in high-fat-diet-induced obeserat. 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 obeserats, 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. CONCLUSION:Cardiac dysfunction of obeserats could be improved by reducing FFAs level. Intramyocardial lipid accumulation may increase the risk of heart failure in obeserats by increasing renin-angiotensin systems activity and protein levels of NF-κB and iNOS in myocardium.
Authors: Luc Djoussé; David Benkeser; Alice Arnold; Jorge R Kizer; Susan J Zieman; Rozenn N Lemaitre; Russell P Tracy; John S Gottdiener; Dariush Mozaffarian; David S Siscovick; Kenneth J Mukamal; Joachim H Ix Journal: Circ Heart Fail Date: 2013-08-07 Impact factor: 8.790