Previous studies from this laboratory have demonstrated an age-related decrease in hepatic malic enzyme (ME) levels and in the response of ME to triiodo-l-thyronine (T3). Moreover, we have recently shown a synergistic interaction of T3 and a high carbohydrate diet in the induction of this enzyme. Studies were therefore undertaken to assess the response of aging rats to a high carbohydrate diet and to test the effect of such dietary manipulations on the responsiveness of ME to T3. For this purpose, a new radio-immunoassay for ME was developed that, because of a 10-fold higher sensitivity, was particularly suited to the measurement of the low concentrations of hepatic enzyme in older animals. The level of ME per milligram of DNA fell ∼70% between 1 and 6 mo with only minor further changes demonstrated between 6 and 18 mo. In contrast, the level of ME per milligram DNA in brain was slightly increased in the older animals. Although the absolute increment of hepatic ME resulting from seven daily injections of T3 (15 μg/100 g body wt) fell with age, the ratio of the ME content per milligram DNA to that observed in control animals maintained on a regular chow diet remained relatively constant with an average value of 11.1. The responsivity of hepatic ME to a high carbohydrate, fat-free diet also decreased with age and could not be attributed exclusively to a reduction in food consumption. The age-related reduction in ME responsivity to dietary stimuli appeared to be due to a reduction in the formation of the specific messenger, (m)RNA for ME as determined in an in vitro translational assay. Our data are consistent with the following hypothesis. There is an age-related decreased hepatic responsivity to a high carbohydrate dietary stimulus. Thyroid hormone administration, as previously postulated by us, interacts with a product or an intermediate of carbohydrate metabolism in a multiplicative fashion. As a consequence, the absolute increment of ME induced by T3 administration also declines with age.
Mary Ann Forciea, Harold L. Schwartz, Howard C. Towle, Cary N. Mariash, F. E. Kaiser, J. H. Oppenheimer