Atorvastatin and fenofibrate increase apolipoprotein AV and decrease triglycerides by up‐regulating peroxisome proliferator‐activated receptor‐α

Abstract

Background and purpose: Combining statin and fibrate in clinical practice provides a greater reduction of triglycerides than either drug given alone, but the mechanism for this effect is poorly understood. Apolipoprotein AV (apoAV) has been implicated in triglyceride metabolism. This study was designed to investigate the effect of the combination of statin and fibrate on apoAV and the underlying mechanism(s). Experimental approach: Hypertriglyceridaemia was induced in rats by giving them 10% fructose in drinking water for 2 weeks. They were then treated with atorvastatin, fenofibrate or the two agents combined for 4 weeks, and plasma triglyceride and apoAV measured. We also tested the effects of these two agents on triglycerides and apoAV in HepG2 cells in culture. Western blot and reverse transcription polymerase chain reaction was used to measure apoAV and peroxisome proliferatoractivated receptor-a (PPARa) expression. Key results: The combination of atorvastatin and fenofibrate resulted in a greater decrease in plasma triglycerides and a greater increase in plasma and hepatic apoAV than either agent given alone. Hepatic expression of the PPARa was also more extensively up-regulated in rats treated with the combination. A similar, greater increase in apoAV and a greater decrease in triglycerides were observed following treatment of HepG2 cells pre-exposed to fructose), with the combination. Adding an inhibitor of PPARa (MK886) abolished the effects of atorvastatin on HepG2 cells. Conclusions and implications:A combination of atorvastatin and fenofibrate increased apoAV and decreased triglycerides through up-regulation of PPARa.

Peripheral neuropathy in ART-experienced patients: prevalence and risk factors

“…The association may be truly protective, since elevated serum triglycerides have been shown to be a risk factor for SPN both in diabetes mellitus and in HIV (Tesfaye et al 2005; Banerjee et al 2011). Statins might, by lowering serum triglyceride levels (Huang et al 2009), reduce progression to symptomatic SPN. Statins also may lower risk of SPN by reducing macrophage activation (Schönbeck and Libby 2004), which has been implicated in the pathogenesis of HIV-SN (Pardo et al 2001; Purwata, 2011; Hahn et al 2008).…”

The marine‐derived furanone reduces intracellular lipid accumulation in vitro by targeting LXRα and PPARα

“…For Oil Red O staining, cells grown on glass coverslips in six‐well plates were fixed with 4% (w/v) paraformaldehyde at room temperature for 30 minutes and then stained with filtered Oil Red O solution (5 mg/mL in 60% isopropanol) at room temperature for 1 hour. Afterwards, the coverslips were washed with H 2 O for several times, dried and mounted on slides . Lipid‐stained area was captured and quantified using Axio Vert.A1 inverted microscope (Zeiss, Jena, Germany), and images were recorded with an Axiocam 506 colour camera (Zeiss).…”

“…Afterwards, cells were treated with 5 µmol/L of the furanone, 1 µmol/L of T0901317 or 5 µmol/L of fenofibrate dissolved in DMEM supplemented with 10% FBS for an additional 24 hours. For the LXR inhibition experiments, 10 µmol/L of LXR antagonist GSK2033 or SR9243 was added 2 hours before the addition of the furanone . The cells were washed in PBS for 3 times and treated with 0.2 mL of RIPA lysis buffer at 4°C for 30 minutes .…”

Rice Bran Oil Improves Insulin Resistance by Affecting the Expression of Antioxidants and Lipid‐Regulatory Genes

“…The relation between fructose feeding and hepatic expression of PPAR‐α or its sensitive genes is controversial. Some studies have recorded downregulation (Huang et al, ; Nagai et al, ; Roglans et al, ), whereas others reported no change in the expression of hepatic Ppara (Kim, Okubo, Juneja, & Yokozawa, ; Mori, Kondo, Hase, & Murase, ).…”