Regulation of fatty acid synthase expression by cholesterol in human cultured cells.
The regulation of fatty acid synthase (FAS) expression by sterols in a cultured human hepatoblastoma cell line, Hep G2, was studied. When cells were treated with compactin in a medium containing lipoprotein deficient serum, FAS mRNA level increased 1.6-fold. A squalene synthase inhibitor, TAN1607A, decreased both free and esterified cholesterol contents in Hep G2 cells and increased mRNA levels for FAS, HMG-CoA reductase, squalene synthase and LDL receptor. However, for the increment of FAS mRNA, a 10-fold higher concentration of this inhibitor was needed. These results demonstrate that the concentration of cellular cholesterol which regulates FAS expression is necessarily lower than the levels which regulate other sterol sensitive genes. FAS mRNA was also increased by an inhibitor of SREBP degradation as well as chenodeoxycholic acid. These results indicate that FAS mRNA expression is regulated by cholesterol and is mediated through SREBPs. The implications of the different modes of sterol regulation of FAS and LDL receptor expression are discussed.
Kawabe
Y
Y
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Sato
R
R
Matsumoto
A
A
Honda
M
M
Wada
Y
Y
Yazaki
Y
Y
Endo
A
A
Takano
T
T
Itakura
H
H
Kodama
T
T
D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002460:Cell Line; D002784:Cholesterol / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D013186:Farnesyl-Diphosphate Farnesyltransferase / Q000037:antagonists & inhibitors; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018197:Hepatoblastoma; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D007700:Kinetics; D008113:Liver Neoplasms; D012333:RNA, Messenger / Q000096:biosynthesis; D011973:Receptors, LDL / Q000096:biosynthesis; D014233:Tricarboxylic Acids / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000096:biosynthesis
D019086:Bridged Bicyclo Compounds, Heterocyclic; D004791:Enzyme Inhibitors; D006888:Hydroxycholesterols; D012333:RNA, Messenger; D011973:Receptors, LDL; C098501:TAN 1607A; D014233:Tricarboxylic Acids; D019014:fas Receptor; C007997:25-hydroxycholesterol; D002784:Cholesterol; D064429:Fatty Acid Synthases; D013186:Farnesyl-Diphosphate Farnesyltransferase