Peroxisome proliferator-activated receptor-α activator fenofibrate prevents high-fat diet-induced renal lipotoxicity in spontaneously hypertensive rats

摘要: We investigated the effects of a high-fat (HF) diet and peroxisome proliferator-activated receptor (PPAR)-alpha activation on intrarenal lipotoxicity associated with renin-angiotensin system (RAS) oxidative stress using spontaneously hypertensive (SHR) rats. Male SHR Wistar-Kyoto (WKY) rats at 8 weeks age were fed either normal-fat or an HF without fenofibrate treatment for 12 weeks. Severe lipid accumulation was noted in than WYK (P<0.05). This 70% decrease renal PPARalpha expression rats, whereas increased WKY by threefold. An also activated intrarenal, not systemic, RAS induced reduced nitric oxide (NO) bioavailability. By contrast, attenuated weight gain, fat mass insulin resistance. Fenofibrate recovered diet-induced decreases accumulation, abolished SHR-HF animals (P<0.01). These activities conferred protection against blood pressure (BP), glomerulosclerosis inflammation. Intrarenal free fatty acid triglyceride concentrations positively correlated angiotensin II (gamma=0.63, 0.36) 24-h urinary 8-hydroxy-deoxyguanosine (gamma=0.36, 0.39), negatively contents (gamma=-0.47, -0.44; P<0.05). depletion aggravated BP inflammation as result stress. Therefore, intervention activators can effectively prevent