The fibrates (isobutyric acid derivatives) primarily activate lipoprotein lipase which is a key enzyme in the degradation of VLDL resulting in lowering of circulating TGs. This effect is of the fibrates is exerted through paroxisome proliferator-activated receptor ci (PPARc) that is a gene transcription regulating receptor expressed in liver, fat and muscles. Activation of PPARct enhances lipoprotein lipase synthesis and fatty acid oxidation. PPARc may also mediate enhanced LDL receptor expression in liver seen particularly with second generation fibrates. Fibrates decrease hepatic TC synthesis as well. A peripheral effect reducing circulating free fatty acids has also been shown.

Drugs in fibrates class primarily lower TG levels by 20—50%, generally accompanied by 10—15% decrease in LDL-CH and a 10—15% increase in HDL-CH. In some patients with hypertriglyceridaemia LDL-CH may rise, partly because of inability of LDL receptor to clear the excess number of LDL particles generated by enhanced VLDL catabolism. The increase in HDL-CH is at least in part due to transfer of surface lipid components from catabolized VLDL to HDL, and partly due to increased production of HDL apoproteins (apo A-I, apo A-IT) by liver. Gemfibrozil a fibrate also appears to reduce VLDL secretion by liver.

LDL composition may be altered with the use of fibrates. Gemfibrozil and bezafibrate have been shown to shift small dense LDL particles (believed to be more atherogenic) to larger less dense particles.

Clofibrate was among the most widely used fibrates, but later evidence showed that it does not prevent atherosclerosis, therefore has gone out of use.

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