Some quantitative changes in iodothyronine distribution and metabolism in mild obesity and aging

Effects of high fat diet (HFD)-induced obesity and moderate aging on iodothyronine kinetics were studied in young adult (3 month old) chow-fed male rats and two groups of older 9- to 11-month-old) male rats, one on chow and the other on HFD. Labeled T4, T3, and rT3 were each injected via an intraatrial double lumen catheter in unanesthetized rats. Serial blood samples were collected according to optimally designed schedules, and labeled iodothyronines in serum were quantified with three different Sephadex gel chromatographic systems. Comprehensive kinetic analyses indicated the following. Several T4 metabolic indices were markedly different between the two older groups (chow vs. HFD), most notable, increased plasma T4 clearance rate (0.098 vs. 0.15 ml/min), decreased plasma T4 concentration (23 vs. 15 ng/ml), and a plasma T4 fractional turnover rate 2 times greater (0.10 vs. 0.19/min), all in the HFD group. There was also a high negative correlation between T4 concentration and body weight (r = 0.77), but not with age. However, the three groups manifested no significant differences in T4 secretion rates (2.0 vs. 2.2 vs. 2.3 ng/min) or whole body pool sizes (2.1 vs. 2.3 vs. 2.4 micrograms). Accounting for metabolic body size, there still were no differences in T4 secretion rate or pool sizes. For T3, we found an almost 3-fold increase in T3 whole body production rates, and a greater than 2-fold increase (from about 25% to 60%) in the percentage of T4 converted to T3 in both older groups relative to that in the young rats. There were almost no significant differences in T3 kinetics between older HFD and older chow-fed groups, and differences in rT3 kinetics among the three groups revealed no clear pattern. Our results suggest that age-related correlations in T4 concentration are a consequence of body weight differences, not age as such. However, the metabolic fate of T4 changes with age, with more than twice as much converted to T3 in older animals. Constancy of T4 production rate and total pool size in young and older animals, independent of body weight, together with the apparent increase in T4 conversion to T3 suggest that the metabolic needs of the animal are being met by regulation of T3 production from T4 conversion, not by regulation of T4 production as such.