title: Atorvastatin and pitavastatin enhance lipoprotein lipase production in L6 skeletal muscle cells through activation of adenosine monophosphate-activated protein kinase.
abstract: 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 1 μmol/L, but neither statin had an effect at 10 μmol/L. We measured AMPK to clarify the mechanism by which statins increase LPL production in skeletal muscle cells. At 1 μmol/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.
authors.affiliation: Center for Diabetes, Metabolism and Endocrinology, Sakura Hospital, Toho University Medical Center, 564-1 Shimoshizu, Sakura-City, Chiba 285-0841, Japan. oohira-04@sakura.med.toho-u.ac.jp
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ohira
authors.forename: Kei
authors.initials: K
authors.lastname: Endo
authors.forename: Atsuhito
authors.initials: A
authors.lastname: Saiki
authors.forename: Yoh
authors.initials: Y
authors.lastname: Miyashita
authors.forename: Kensuke
authors.initials: K
authors.lastname: Terai
authors.forename: Takeyoshi
authors.initials: T
authors.lastname: Murano
authors.forename: Fusako
authors.initials: F
authors.lastname: Watanabe
authors.forename: Ichiro
authors.initials: I
authors.lastname: Tatsuno
authors.forename: Kohji
authors.initials: K
authors.lastname: Shirai
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D000069059:Atorvastatin; D002478:Cells, Cultured; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D008798:Mevalonic Acid / Q000494:pharmacology; D018482:Muscle, Skeletal / Q000378:metabolism*; D011758:Pyrroles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D012333:RNA, Messenger; D000069059:Atorvastatin; D055372:AMP-Activated Protein Kinases; D008071:Lipoprotein Lipase; C108475:pitavastatin; D008798:Mevalonic Acid