The orphan nuclear receptor, small heterodimer partner (SHP), appears to play a negative regulatory role in innate immune signaling. Emerging evidence warrants further study on the therapeutic targeting of SHP to suppress excessive and deleterious inflammation. Here we show that fenofibrate, which targets SHP, is required for inhibiting systemic inflammation via mitochondrial uncoupling protein...

OBJECTIVE To demonstrate, quantify, and mechanistically dissect antiatherosclerotic effects of fenofibrate besides lowering plasma cholesterol per se. METHODS AND RESULTS ApoE*3Leiden transgenic mice received either a high-cholesterol diet (HC) or HC containing fenofibrate (HC+FF) resulting in 52% plasma cholesterol-lowering. In a separate low-cholesterol diet (LC) control group, plasma chole...

Oxidative stress has been implicated in neurodevelopmental theories of schizophrenia. Antioxidant Peroxysome Proliferator-Activated Receptors α (PPARα) agonist fenofibrate has neuroprotective properties and could reverse early preclinical infringements that could trigger the illness. We have evaluated the neuroprotective interest of fenofibrate in a neurodevelopmental rat model of schizophrenia...

Rhabdomyolysis associated with fenofibrate monotherapy is extremely rare. Here, we report a rare case of rhabdomyolysis of the psoas muscle in an 82-year-old man with chronic myelogenous leukemia (CML). He was prescribed fenofibrate because of a hypertriglyceridemia. The patient reported generalized muscle pain and right abdominal pain while receiving fenofibrate monotherapy. An abdominal compu...

Fibrates, including fenofibrate, exert their biological effects by binding peroxisome proliferator-activated receptor alpha (PPARalpha), a member of the nuclear receptor superfamily of ligand-activated transcription factors. Treatment with PPARalpha agonists enhances fatty acid oxidation, decreases plasma triglycerides, and may promote reverse cholesterol transport. In addition, fibrate adminis...

In a recent FIELD study the fenofibrate therapy surprisingly failed to achieve significant benefit over placebo in the primary endpoint of coronary heart disease events. Increased levels of atherogenic homocysteine were observed in some patients assigned to fenofibrate therapy but the molecular mechanisms behind this are poorly understood. Herein we investigated HDL lipidomic profiles associate...

The drug fenofibrate has received major attention as a novel medical treatment for diabetic retinopathy (DR) and other diabetes-induced microvascular complications. This interest stems from two recent large, well-designed clinical trials that demonstrated large reductions in the progression of DR and the need for laser intervention, in addition to a reduction in renal and neurological outcomes,...

hLpL(GPI) transgenic mice that overexpress human lipoprotein lipase (hLpL) with a glycosylphosphatidylinositol anchor on cardiomyocytes develop lipotoxic cardiomyopathy associated with increased cardiac uptake of plasma lipids. We hypothesized that peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, or a PPARalpha/gamma agonist would alter cardiac function by modulating lipid upt...

Zhao, Xueying, Jeffrey E. Quigley, Jianghe Yuan, Mong-Heng Wang, Yiqing Zhou, and John D. Imig. PPARactivator fenofibrate increases renal CYP-derived eicosanoid synthesis and improves endothelial dilator function in obese Zucker rats. Am J Physiol Heart Circ Physiol 290: H2187–H2195, 2006. First published February 24, 2006; doi:10.1152/ajpheart.00937.2005.—Previous studies have shown that the s...

A large elevation in serum creatinine (S(Cr)) on an unchanged peritoneal dialysis (PD) schedule is usually caused by a decrease in total creatinine clearance (C(Cr)), but may also reflect an increase in creatinine (Cr) production. A meticulously compliant 43-year-old man with lupus nephritis on automated nocturnal PD plus an additional daytime exchange developed a rise in S(Cr) to 16.73 mg/dL f...