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.
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The clinically used drugs with known PGC-1α-modulating activity, such as fibrates, thiazolidinediones, metformin, and statins, display neurotoxicity and a limited ability to cross the blood-brain barrier.
“The clinically used drugs with known PGC-1α-modulating activity, such as fibrates, thiazolidinediones, metformin, and statins, display neurotoxicity and a limited ability to cross the blood–brain barrier (BBB) [35,36,37,38].”
From Protective Effects of PGC-1α Activators on Ischemic Stroke in a Rat Model of Photochemically Induced Thrombosis (2021) · cites this paper as [38]
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- Authors
- Ohira, M., Endo, K., Saiki, A., Miyashita, Y., Terai, K., Murano, T., Watanabe, F., Tatsuno, I., & Shirai, K.
- Affiliations
- Toho University Medical Center Sakura Hospital (JP)
- Corresponding author
- Ohira, Masahiro
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 61
- Issue
- 10
- Pages
- 1452-1460
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W1967501240
- Cited by
- 25
- References
- 44
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 5 · 2022: 2 · 2021: 3 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 2 · 2014: 3
- FWCI
- 1.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Keywords
- atorvastatin, pitavastatin, lipoprotein lipase, AMPK, statins, skeletal muscle cells, L6 myoblasts, mevalonate, compound C
- MeSH terms
- Atorvastatin, Animals, Cells, Cultured, Heptanoic Acids, Lipoprotein Lipase, Mevalonic Acid, Pyrroles, Quinolines, RNA, Messenger, Muscle, Skeletal, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Rats, AMP-Activated Protein Kinases, Real-Time Polymerase Chain Reaction
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