Induction of lipoprotein lipase gene expression in 3T3-L1 preadipocytes by atorvastatin, a cholesterol- and triglyceride-lowering drug.
Atorvastatin is a drug of choice in the treatment of coronary heart disease, because this hepatic 3-hydroxy-3-methylglutaryl coenzyme reductase inhibitor significantly decreases plasma cholesterol and triglyceride levels. However, little is known about the underlying molecular targets of this drug. Lipoprotein lipase (LPL), an enzyme with multiple functions in non-hepatic lipid metabolism, may be a potential candidate and LPL gene expression may increase in response to a treatment with atorvastatin. In order to verify this hypothesis, mouse 3T3-L1 preadipocytes were incubated with 1 and 10 micromol/l atorvastatin for 24 and 48 h and LPL mRNA concentration was measured by reverse transcription-polymerase chain reaction. Our data indicated that atorvastatin increased LPL mRNA concentration by a time- and dose-dependent mechanism. LPL mRNA concentration was significantly increased by 82% with 10 micromol/l atorvastatin after 48 h. LPL mRNA concentration was 28% greater (not significant) than control with 10 micromol/l atorvastatin after 24 h. No increase was obtained with 1 micromol/l atorvastatin after 24 or 48 h. The first 976 nucleotides of rat LPL promoter were transfected in 3T3-L1 preadipocytes. Addition of 10 micromol/l atorvastatin for 48 h resulted in a 44% increase of rat LPL promoter activity. This study demonstrates for the first time that a statin can regulate LPL gene expression transcriptionally in preadipocytes.
Bey
Lionel
L
Biomedical Sciences, University of Missouri-Columbia, Mo 65211, USA.
Maigret
Pascal
P
Laouenan
Hervé
H
Hamilton
Marc T
MT
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000069059:Atorvastatin; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression; D006538:Heptanoic Acids / Q000494:pharmacology*; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008071:Lipoprotein Lipase / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D013997:Time Factors
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D011758:Pyrroles; D012333:RNA, Messenger; D000069059:Atorvastatin; D008071:Lipoprotein Lipase