Modulation of fatty acid metabolism is involved in the alleviation of isoproterenol-induced rat heart failure by fenofibrate.
Heart failure is a disease predominantly caused by an energy metabolic disorder in cardiomyocytes. The present study investigated the inhibitory effects of fenofibrate (FF) on isoproterenol (ISO)‑induced hear failure in rats, and examined the underlying mechanisms. The rats were divided into CON, ISO (HF model), FF and FF+ISO (HF animals pretreated with FF) groups. The cardiac structure and function of the rats were assessed, and contents of free fatty acids and glucose metabolic products were determined. In addition, myocardial cells were isolated from neonatal rats and used in vitro to investigate the mechanisms by which FF relieves heart failure. Western blot analysis was performed to quantify the expression levels of peroxisome proliferator‑activated receptor (PPAR)α and uncoupling protein 2 (UCP2). FF effectively alleviated the ISO‑induced cardiac structural damage, functional decline, and fatty acid and carbohydrate metabolic abnormalities. Compared with the ISO group, the serum levels of brain natriuretic peptide (BNP), free fatty acids, lactic acid and pyruvic acid were decreased in the FF animals. In the cultured myocardial cells, lactic acid and pyruvic acid contents were lower in the supernatants obtained from the FF animals, with lower levels of mitochondrial ROS production and cell necrosis, compared with the ISO group, whereas PPARα upregulation and UCP2 downregulation occurred in the FF+ISO group. The results demonstrated that FF efficiently alleviated heart failure in the ISO‑induced rat model, possibly via promoting fatty acid oxidation.
Department of Cardiovascular Medicine, The 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Ping
P
Li
Department of Cardiology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, Jiangxi 341000, P.R. China.
Shike
S
Luo
Department of Cardiovascular Medicine, The 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Chunji
C
Pan
Department of Cardiovascular Medicine, The 2nd Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
Xiaoshu
X
Cheng
D000818:Animals; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism*; D011345:Fenofibrate / Q000494:pharmacology* / Q000627:therapeutic use; D006333:Heart Failure / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D000960:Hypolipidemic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D007473:Ion Channels / Q000378:metabolism; D007545:Isoproterenol; D008297:Male; D024101:Mitochondrial Proteins / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D009336:Necrosis; D047493:PPAR alpha / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D000071246:Uncoupling Protein 2
D005227:Fatty Acids; D000960:Hypolipidemic Agents; D007473:Ion Channels; D024101:Mitochondrial Proteins; D047493:PPAR alpha; D017382:Reactive Oxygen Species; C000604391:Ucp2 protein, rat; D000071246:Uncoupling Protein 2; D007545:Isoproterenol; D011345:Fenofibrate