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Atorvastatin and pitavastatin enhance lipoprotein lipase production in L6 skeletal muscle cells through activation of adenosine monophosphate-activated protein kinase.
Metabolism. 2012 Oct; 61(10):1452-60.M

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+Show Affiliations

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.jpNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22520230

Citation

Ohira, Masahiro, et al. "Atorvastatin and Pitavastatin Enhance Lipoprotein Lipase Production in L6 Skeletal Muscle Cells Through Activation of Adenosine Monophosphate-activated Protein Kinase." Metabolism: Clinical and Experimental, vol. 61, no. 10, 2012, pp. 1452-60.
Ohira M, Endo K, Saiki A, et al. Atorvastatin and pitavastatin enhance lipoprotein lipase production in L6 skeletal muscle cells through activation of adenosine monophosphate-activated protein kinase. Metabolism. 2012;61(10):1452-60.
Ohira, M., Endo, K., Saiki, A., Miyashita, Y., Terai, K., Murano, T., Watanabe, F., Tatsuno, I., & Shirai, K. (2012). Atorvastatin and pitavastatin enhance lipoprotein lipase production in L6 skeletal muscle cells through activation of adenosine monophosphate-activated protein kinase. Metabolism: Clinical and Experimental, 61(10), 1452-60. https://doi.org/10.1016/j.metabol.2012.03.010
Ohira M, et al. Atorvastatin and Pitavastatin Enhance Lipoprotein Lipase Production in L6 Skeletal Muscle Cells Through Activation of Adenosine Monophosphate-activated Protein Kinase. Metabolism. 2012;61(10):1452-60. PubMed PMID: 22520230.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atorvastatin and pitavastatin enhance lipoprotein lipase production in L6 skeletal muscle cells through activation of adenosine monophosphate-activated protein kinase. AU - Ohira,Masahiro, AU - Endo,Kei, AU - Saiki,Atsuhito, AU - Miyashita,Yoh, AU - Terai,Kensuke, AU - Murano,Takeyoshi, AU - Watanabe,Fusako, AU - Tatsuno,Ichiro, AU - Shirai,Kohji, Y1 - 2012/04/19/ PY - 2011/04/28/received PY - 2012/03/19/revised PY - 2012/03/20/accepted PY - 2012/4/24/entrez PY - 2012/4/24/pubmed PY - 2012/12/10/medline SP - 1452 EP - 60 JF - Metabolism: clinical and experimental JO - Metabolism VL - 61 IS - 10 N2 - 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. SN - 1532-8600 UR - https://www.unboundmedicine.com/medline/citation/22520230/Atorvastatin_and_pitavastatin_enhance_lipoprotein_lipase_production_in_L6_skeletal_muscle_cells_through_activation_of_adenosine_monophosphate_activated_protein_kinase_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0026-0495(12)00112-6 DB - PRIME DP - Unbound Medicine ER -