Acyl-CoA synthetase mRNA expression is controlled by fibric-acid derivatives, feeding and liver proliferation.
Several enzymes of the beta-oxidation pathway have been shown to be induced after stimulation with peroxisomal proliferators, including several hypolipidemic drugs. We investigated the regulation of the long-chain-acyl-CoA synthetase (ACS) gene in the liver. Fenofibrate, a hypolipidemic drug and potent peroxisomal proliferator, induced ACS gene expression in several tissues. In liver, large increases in ACS mRNA levels and ACS activity were observed after fenofibrate administration. Adipose tissue ACS mRNA levels and ACS activity were also stimulated upon fibrate treatment but to a lesser extent in comparison with liver ACS mRNA. Kidney ACS mRNA was only weakly induced, except for the highest dose and the longest treatment period, where a strong induction was observed. In contrast to these tissues, heart ACS mRNA and ACS activity remained almost unchanged after fenofibrate treatment. These effects of fenofibrate could be reproduced by other fibrates such as clofibrate. In addition, it is demonstrated that both nutritional composition and liver proliferation trigger ACS gene expression in liver. Consequently, these data suggest that ACS is a highly regulated enzyme with a potentially important control function in lipid metabolism.
Schoonjans
K
K
Laboratoire de Biologie des Régulations chez les Eucaryotes, Université de Nice-Sophia Antipolis, France.
Staels
B
B
Grimaldi
P
P
Auwerx
J
J
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002994:Clofibrate / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000235:genetics*; D004032:Diet; D011345:Fenofibrate / Q000494:pharmacology; D015248:Gemfibrozil / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005938:Glucocorticoids / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental; D008297:Male; D051379:Mice; D008830:Microbodies / Q000201:enzymology; D009206:Myocardium / Q000378:metabolism; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014407:Tumor Cells, Cultured; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D005938:Glucocorticoids; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase; D002994:Clofibrate; D015248:Gemfibrozil; D011345:Fenofibrate