Gemfibrozil expression

The fibrates are another class of antihyperlipidemic drug and are frequently coadministered with a statin. Fibrates act as agonists of the peroxisome proliferator-activated receptors (PPAR), particularly PPAR-a. PPARs are nuclear receptors that influence gene expression and lipid metabolism. Examples of fibrates include gemfibrozil (Lopid, A.110) and fenofibrate (Tricor, A.lll) (Figure A.30). Fenofibrate is hydrolyzed in the body to its active form, fenofibric acid (A.112). Fibrates do not decrease LDL levels as effectively as statins, but fibrates do elevate HDL cholesterol levels. 

Several pharmacogenomic studies, mainly in animal models, have characterized the molecular mechanisms contributing to the lipidlowering effect of fibrates. Hepatic transcription profiling of clofibrate or gemfibrozil-treated WT rats demonstrated increased expression of many genes involved in beta-oxidation, as well as FFA and cholesterol synthesis, including fatty acyl-Coenzyme A oxidase [45, 191, 192], acetyl-Coenzyme A acetyltransferase... 

Fig. 5. Effects of carbamazepine (CBZ) and gemfibrozil (GEM) on relative growth hormone (GH) mRNA expression levels in goldfish pituitary. Data represent means standard errors with n = 10. C, control < 0.05 compared with C by one-way ANOVA Tukey post hoc test.

Increased expression of high-affinity LDL receptors Increased lipid hydrolysis by lipoprotein lipase Inhibition of secretion of VLDL by the liver Reduction of secretion of HDL by the liver When used as monotherapy, a major toxicity of gemfibrozil is increased risk of (A) Bloating and constipation Cholelithiasis Hyperuricemia Liver damage Severe cardiac arrhythmia... 

Overall, fibrates decrease plasma triglyceride levels much more dramatically than they decrease plasma cholesterol levels. They significantly decrease VLDL levels, cause a moderate Increase In HDL levels, and have variable effects on LDL concentrations. As an example of this latter point, gemfibrozil will raise LDL levels In patients with hypertriglyceridemia but lower LDL levels in patients with normal triglyceride levels. The exact mechanisms for these actions have not been fully elucidated however, studies have shown that this class of compounds can produce a variety of beneficial effects on lipoprotein metabolism. Many of these effects have been proposed to be mediated through the activation of peroxisome proliferator-activated receptors (PPARs) and an alteration of gene expression. Specifically, fibrates bind to PPARa (7,15,27,44). 

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