Atorvastatin Increases Lipoprotein Lipase Expression in vitro and Activity in vivo

Recently, Saiki et al. (1) reported an enhanced Lipoprotein Lipase (LPL)-activity and expression in preadipocytes mediated by pitavastatin treatment.They state initially that the mechanism by which statins reduce triglycerides is thought to be due to the reduced VLDL-secretion from the liver (2), whereas little data about the catabolism of lipoproteins was available.In fact, therapy with statins is associated with a decrease in triglycerides, but the mechanisms by which statins lower triglyceride levels are not exactly known.This effect and the particular benefit of a statin therapy for diabetic patients suggest an involvement of LPL.In addition to pitavastatin, various other statins (pravastatin, simvastatin, atorvastatin) were tested by Saiki et al. (1) for their ability to increase LPL-activity in vitro, but surprisingly only simvastatin and pitavastatin (-30%) increased LPL-activity.Pitavastatin treatment also resulted in a 42%-increase of LPL-protein and a 26%-increase in LPL-message.Finally, pioglitazone added to the culture media increased LPL-activity with an additional increase of LPL-activity when pitavastatin was added that, in turn, could be prevented by pre-incubation with mevalonate.The authors concluded from their study that the increased LPL-activity by pitavastatin treatment in vitro may not be mediated by a PPARγ-dependent mechanism, and that this pitavastatin-driven effect may be different from the triglyceride lowering effect of other statins.The conclusions made in this detailed study do partly complement the observations made in previous studies.However, we think that the statin effect on LPL is not restricted to pitavastatin or simvastatin.It has been shown that atorvastatin is able to induce LPL gene expression in 3T3-L1 pre-adipocytes (3).Moreover, atorvastatin and pravastatin elevated pre-heparin lipoprotein lipase mass of type 2 diabetics with hypercholesterolemia (4), although the measurement of pre-heparin LPL-activity is of uncertain significance.Our own study revealed a 25%increase of LPL-activity in type 2 diabetic patients by atorvastatin (5).We obtained similar results when evaluating the effect of pravastatin (Schneider J.G. et al., unpublished).In rabbits, statin treatment resulted in a 72% increase in LPL activity (6).Interestingly, for pitavastatin, no LPL-mediated effect on triglycerides has been found