The effects of experimental inflammation on turnover of fatty acid synthetase and levels of fatty acid synthetase messenger RNA in rat liver.
Suppression, by experimental inflammation, induced by subcutaneous injection of oil of turpentine, of the usual increase in liver fatty acid synthetase (FAS) activity resulting from fat-free feeding following starvation (adaptive synthesis) was shown to result entirely from lowered hepatic content of FAS protein. Comparison of changes in the relative rate of synthesis of FAS, determined radioimmunochemically during adaptive synthesis with and without inflammation, with concomitant changes in FAS activity, revealed that inflammation partically suppressed the increased rate of synthesis characteristic of adaptive synthesis, but insufficiently to account entirely for the suppression of enzyme activity. Inflammation accelerated the relative rate of degradation of FAS, causing a 50% decrease in enzyme half-life and a corresponding increase in kd and turnover index. Levels of translatable FAS mRNA rose only fivefold after 24 h of adaptive synthesis, while the relative rate of FAS synthesis increased 12-fold indicating the operation of both transcriptional and translational control. Inflammation, induced at the start of adaptive synthesis, caused a 65% lowering of the relative rate of FAS synthesis after 24 h and a 60% decrease in mRNA translatable as FAS, but was without effect on the total translational activity of the mRNA although alterations in the size distribution of RNA species in the mRNA fraction were noted.
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D004041:Dietary Fats / Q000008:administration & dosage*; D064429:Fatty Acid Synthases / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D011061:Poly A / Q000378:metabolism; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D013217:Starvation; D014158:Transcription, Genetic; D014425:Turpentine
D004041:Dietary Fats; D012333:RNA, Messenger; D011061:Poly A; D064429:Fatty Acid Synthases; D014425:Turpentine