Carbohydrate-dependent induction of fatty acid synthase in primary cultures of rat hepatocytes.
The glucose and insulin-dependent long-term regulation of fatty acid synthase was studied in primary cultures of hepatocytes from adult female rats. Under basic culture conditions, i.e. 5.5 mM glucose and 0.5 nM insulin, the enzyme activity was continuously decreased over 6 days. In the presence of 100 nM insulin this decrease was reduced but it was not prevented. Enhancement of glucose to 20 mM was followed by an increase of the enzyme activity; after 5 days of treatment the activity was three times higher than under basic culture conditions. The simultaneous presence of 20 mM glucose and of 100 nM insulin resulted in a much more pronounced increase of the activity; after 5 days of treatment the activity was eight times higher than under basic culture conditions. The enhancement was prevented by inhibition of glycolysis. This may indicate that the increase of fatty acid synthase was mediated by a metabolite of glucose rather than by glucose itself. The coordinate regulation of fatty acid synthase and of other lipogenic enzymes was specific as demonstrated by comparison with the activity of lactate dehydrogenase and with synthesis and degradation of cytosolic proteins. The enhancement of the enzyme protein, demonstrated by rocket immunoelectrophoresis, was due to an increase in the rate of enzyme synthesis by 600% as well as to a prolongation of the apparent half-life of the enzyme by 50% (45 h).
D000818:Animals; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D064429:Fatty Acid Synthases / Q000096:biosynthesis*; D005260:Female; D005947:Glucose / Q000494:pharmacology*; D007122:Immunoelectrophoresis / Q000379:methods; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000201:enzymology*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D064429:Fatty Acid Synthases; D005947:Glucose