The age-related changes in lipogenic enzymes: the role of dietary factors and thyroid hormone responsiveness

To determine whether resistance to insulin or to thyroid hormones rather th an an inherent defect in enzyme activity expression account for the age-rel ated changes in lipogenic enzymes, the activities of malic enzymes (ME), fa tty acid synthase (FAS), glucose-6-phosphate dehydrogenase (G-6PD) and 6-ph osphogluconate dehydrogenase (6-PGD) were assayed in hepatic, retroperitone al fat and epididymal fat cytosol of male Fischer 344 rats at 3.5, 12 and 2 5 months of age. The rats were maintained on either regular rat chow with 6 2% of calories as complex carbohydrates or were given either high glucose o r fructose diet with 65.7% of calories provided by glucose or fructose resp ectively. Additional groups of young and aged rats were treated with L-trii odothyronine (T-3) (15 mu g/100 g body weight) for 10 days. Treatment with T-3 resulted in higher levels of hepatic ME activity regardless of the diet consumed or the age of the rats. T-3 had no consistent effect on FAS, G-6P D or 6-PGD activities. ME response to T-3 in young rats was significantly g reater than that found in aged rats regardless of diet. The age-related dec rease in basal hepatic ME activity was not apparent in rats maintained on t he high glucose or the high fructose diets, yet the T-3 responsiveness of M E in rats maintained on these diets was not normalized. In adipose tissue, with the exception of the age-related changes in basal activity of the lipo genic enzymes, neither T-3 nor the feeding of the test diets had any consis tent effects. Since insulin resistance induced by high fructose feeding did not reduce hepatic lipogenic enzymes, it is unlikely that the age-related increase in insulin resistance explains the reduced lipogenic enzyme activi ty in aged rats. However, resistance to thyroid hormone action found in age d rats may partly account for the reduced hepatic lipogenic enzyme activity . (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.