Ohira_2012_Metabolism_61_1452

Pravastatin and atorvastatin increase the serum level of lipoprotein lipase LPL mass in vivo but do not increase LPL activity in 3T3-L1 preadipocytes in vitro LPL is mainly produced by adipose tissue and skeletal muscle cells Metformin enhances LPL in skeletal muscle through adenosine monophosphate-activated protein kinase AMPK activation but not in adipocytes This study aimed to examine the effect of 3-hydroxy-3-methylglutaryl coenzyme A HMG-CoA reductase inhibitors statins on LPL production and to investigate the mechanism by which statins enhance skeletal muscle cell LPL production L6 skeletal muscle cells were incubated with pravastatin simvastatin atorvastatin or pitavastatin LPL activity protein levels and mRNA expression were measured Atorvastatin and pitavastatin significantly increased LPL activity protein levels and mRNA expression in L6 skeletal muscle cells at 1mumol/L but neither statin had an effect at 10mumol/L We measured AMPK to clarify the mechanism by which statins increase LPL production in skeletal muscle cells At 1mumol/L both atorvastatin and pitavastatin enhanced AMPK activity but this enhancement was abolished when AMPK signaling was blocked by compound C The increased expressions of LPL protein and mRNA by atorvastatin and pitavastatin were reduced by compound C In addition mevalonic acid abolished atorvastatin and pitavastatin-induced AMPK activation and LPL expression These results suggest that atorvastatin and pitavastatin increase LPL activity protein levels and LPL mRNA expression by activating AMPK in skeletal muscle cells.