Experimental Studies on the Hormonal Regulation of Lipid Metabolism by Using Carbon<SUP>14</SUP> Labeled Substances

The influence of altered adrenocortical activity on the in vivo incorporation of acetate1-¹⁴C or palmitate-1-¹⁴C into fatty acids and cholesterol in the rat liver, epididymal adipose tissue and plasma was studied over the period ranging from 15 minutes to 24 hours. It was also undertaken to examine the action of adrenocorticotropic hormone (ACTH) in lipid metabolism by observing the effects of the administration of ACTH to adrenalectomized rats. Male Wistar rats weighing 140 to 150 gm were divided into 6 groups : adrenalectomized rats (operated 7 days prior to sacrifice), intact rats given 5 mg of cortisone acetate daily for 7 days, adrenalectomized rats given 1 mg of cortisone acetate per 100 gm of body weight daily for 5 days, intact rats given 4 I.U. of ACTH (ACTH-Z) daily for 7 days, adrenalectomized rats given 4 I.U. of ACTH daily for 7 days and nontreated control. Fatty acids and cholesterol of tissues and plasma were separated by the method of Srere et al at several time intervals after the intraperitoneal injection of acetate-1-¹⁴C (5 μc per 100 gm of body weight) or palmitate-1-¹⁴C (1 μc per 100 gm of body weight) and radioactivities of these fractions were measured by a gas flow counter. Specific activity was expressed as cpm per mg of each fraction. The cholesterol concentration was determined by the method of Abell et al.<BR>1) The administration of cortisone or ACTH to intact rats increased the cholesterol concentration of plasma, although there was no significant change in that of liver. Adrenalectomy resulted in a decrease in the concentration of plasma cholesterol. In addition, the lower cholesterol concentration of plasma observed in adrenalectomized rats was restored by cortisone substitution. Almost the same tendencies as the data of plasma were observed in epididymal adipose tissue.<BR>2) The specific activity of liver cholesterol 15 minutes after acetate-1-¹⁴C injection was higher in intact rats given cortisone than in nontreated control, while that 6 hours after injection was much lower in the former than in the latter. The markedly depressed hepatic cholesterogenesis found in adrenalectomized rats was restored to normal by cortisone substitution. The cortisone treated groups showed a significantly high value with regard to the specific activity of plasma cholesterol. These results suggest that cortisone accelerates biosynthesis as well as degradation of cholesterol, and that cortisone administration may be associated with hypercholesteremia because of the more marked increase in rates of synthesis and of enhancing liver secretion of cholesterol into plasma.<BR>3) On the other hand, cortisone administration inhibited biosynthesis of fatty acid in the liver, although adrenalectomy did not result in any marked alteration of fatty acid synthesis.<BR>4) A higher initial incorporation of acetate-l-¹⁴C into liver cholesterol and a lower initial incorporation of the same isotope into liver fatty acids occurred in adrenalectomized rats given ACTH, as compared with adrenalectomized control. These results may suggest that ACTH would have a stimulating effect on hepatic cholesterogenesis and an inhibiting effect on hepatic lipogenesis.<BR>5) The specific activity of fatty acids of epididymal adipose tissue 2 hours after palmitate-l-¹⁴C injection was lower in intact rats given cortisone and adrenalectothized rats given ACTH than in nontreated control and adrenalectomized control, respectively. These data for degradation of palmitate-1-¹⁴C in adipose tissue suggest that both cortisone and ACTH have a stimulating effect on lipolysis and fat mobilization.