Effect of dietary polyunsaturated fatty acids on the activity and content of fatty acid synthetase in mouse liver

Abstract

When mice, previously fed a standard laboratory mouse chow diet, were fed a high carbohydrate (50% glucose) diet containing 15% (w/w) hydrogenated cottonseed oil, the activity of hepatic fatty acid synthetase per mg cytosolic protein increased approximately 3-fold over an 11-day period. However, when mice were placed on an isocaloric diet containing 15% (w/w) corn oil, the specific activity of the enzyme did not increase above the chow-fed levels. Using antibody prepared against pure mouse liver fatty acid synthetase, we showed that the increase in the specific activity of fatty acid synthetase in the hydrogenated cottonseed oil-fed animals resulted from an elevation in the hepatic content of the enzyme. This increase was a result of (a) an increase in the rate of synthesis of the enzyme relative to that of total protein and (b) a decrease in the enzyme's degradative rate, when compared to these parameters measured in the livers of the corn oil-fed animals. Furthermore, these dietary-induced changes in enzyme specific activity were not accompanied by changes in the catalytic efficiency of fatty acid synthetase; since both hydrogenated cottonseed oil-fed and corn oil-fed animals showed identical immunoequivalences and contained similar amounts of immunoprecipitable 3H-labeled enzyme protein per unit enzyme activity (in mice pulse-labeled with [ 3H]leucine). The results of experiments in which we administered pure fatty acids (oleic (cis- Δ 9-18:1), ricinoleic (12-hydroxy-cis- Δ 9-18:1), Iinoleic (cis, cis- Δ 9,12-18:2), α-linoleic ( cis, cis, cis- Δ 9,12,15-18:3), columbinic ( trans, cis, cis- Δ 5,9,12-18:3) and arachidonic (all-cis- Δ 5,8,11,14-20:4)) to mice maintained on a 50% glucose diet suggested that the ability of a fatty acid to inhibit hepatic fatty acid synthetase activity and to prevent an increase in hepatic fatty acid synthetase protein was related to the degree and position of unsaturation of the fatty acid administered and not to the ability of the fatty acid to act as prostaglandin precursor. Those 18-carbon fatty acids which possessed a double bond at positions Δ 9,12 (linoleic, columbinic and α-linolenic) were the most effective at inhibiting hepatic fatty acid synthetase activity and in preventing an increase in enzyme content.