Lipoprotein lipases transcription activation

Schoonjans, K, Peinado-Onsurbe, J., Lefebvre, A. M., Heyman, R. A., Briggs, M, Deeb, S., Staels, B., and AuwerxJ. (1996) PPARalpha and PPARgamma Activators Direct a Distinct TissueTSpecific Transcriptional Response via a PPRE in the Lipoprotein Lipase Gene. EMBOJ. 15, 5336-5348. 

Schoonjans K, Peinado-Onsurbe J, Lefebvre AM, Heyman RA, Briggs M, Deeb S, Staels B, Auwerx J. PPARalpha and PPARgamma activators direct a distinct tissue-specific transcriptional response via a PPRE in the lipoprotein lipase gene. EMBO J. 1996 15 5336-5348. 

A. Mechanism and Effects Fibric acid derivatives (eg, gemfibrozil, fenofibrate, clofibrate) are ligands for the peroxisome proliferator-activated receptor-alpha (PPAR-a) protein, a receptor that regulates transcription of genes involved in lipid metabolism. Tbis interaction with PPAR-a results in increased activity of lipoprotein lipase and enhanced clearance of triglyceride-rich lipoproteins (Figure 35-2). Cholesterol biosynthesis in the liver is seeondarily reduced. The fibrates reduce serum triglyceride concentrations (Table 35-3). There may be a small reduction in LDL cholesterol and a small increase in HDL levels. 

Decreases in plasma VLDL primarily result from the ability of these compounds to stimulate the activity of lipoprotein lipase, the enzyme responsible for removing triglycerides from plasma VLDL (Fig. 30.5). Additionally, fibrates can lower VLDL levels through PPARa-mediated stimulation of fatty acid oxidation, inhibition of triglyceride synthesis, and reduced expression of apoC-lll. This latter effect enhances the action of lipoprotein lipase, because apoC-lll normally serves as an inhibitor of this enzyme. Favorable effects on FIDL levels appear to be related to increased transcription of apoA-l and apoA-ll as well as a decreased activity of cholesteryl ester transfer protein. 

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