Comparison of age-related decreases in the basal and carbohydrate inducible levels of lipogenic enzymes in adipose tissue and liver

Abstract

An age-related decrease in the level of four lipogenic enzymes—malic enzyme (ME), fatty acid synthetase (FAS), glucose-6-phosphate dehydrogenase (G-6-PD), and 6-phosphogluconate dehydrogenase (6-PGD)—was compared in the adipose tissue and liver of rats. In adipose tissue the activity of ME per milligram of protein at one month exceeded that observed at one year by a factor of 27 or more. The bulk of the fall occurred between one and three months. Adipose FAS, G-6-PD, and 6-PGD showed a similar but less precipitous age-related decline. The extent of age-related changes in the adipose tissues consistently exceeded those observed in liver preparations from the same animal. For both fat and liver, administration of a high carbohydrate fat-free diet for four days also elicited a substantially greater incremental ME response in young rats than in old animals. The age-related changes in basal ME activity were proportional to the increments produced by dietary stimulation. Thus, as previously proposed by us for liver, the decrease in basal ME in adipose tissue may be the result of a reduced generation from dietary carbohydrate of a stimulus responsible for the induction of lipogenic enzymes. Additional experiments were performed in animals provided with 10% glucose in their drinking water and infused with high doses of insulin for 4 to 12 days. In the fat of older animals, such treatment resulted in the induction of adipose ME activity to levels almost equivalent to those achieved with similar treatment in younger animals. Whereas maximal levels of ME in the younger animals could be attained simply with the glucose in the drinking water, insulin administratin was required in the older animals. Presumably, the insulin response evoked by glucose in the younger animals elicited a maximal ME increment. In the older animals, however, the endogenous insulin response to glucose failed to achieve a comparable degree of ME induction in the fat. Since the concentrations of insulin attained in the older animals were equal to or greater than those attained in the younger rats, both in the basal and the stimulated state, the diminished ME response in the older animals can be considered to be a form of tissue insulin resistance. Diminished glucose metabolism in the adipocytes of older rats is well established even in the presence of normal plasma glucose concentrations. Therefore, the results suggest that the level of hepatic and adipose ME activity may be useful as an index of such changes.