Impaired peripheral thyroid hormone metabolism in genetic obesity.

The obese Zucker rat has alterations in thyroid hormone metabolism resulting in a lower serum T3 concentration and T3 plasma appearance rate compared to its lean littermates. This study was undertaken to measure the contribution of specific nonthyroidal tissues to the total production of T3 in vivo in the Zucker fatty rat. Simultaneous pulse kinetic studies of T4 and T3 were performed in lean and obese Zucker littermates and analyzed according to a three-pool model of distribution and metabolism. The serum concentration and plasma appearance rate of T3 were both decreased in the obese vs. lean Zucker phenotype (P < 0.05) despite an elevated serum concentration and plasma appearance rate for T4. The quantity of T4 within the fast pool (i.e. liver and kidney) available for deiodination was equal for both phenotypes; however, generation of T3 within the fast pool was impaired for the obese compared to the lean group (-25%; P < 0.05). The tissue content of radiolabeled T3 generated within the liver 24 h post injection of T4 for the obese group was 48% lower (P < 0.02) vs. the lean group. A separate group of lean and obese littermates were surgically thyroid-ectomized and replaced with T4 to maintain a euthyroid state. The obese Zucker group had lower serum T3 concentrations and T3 plasma appearance rates compared to similarly treated lean Zucker animals despite similar T4 serum concentrations. Treatment with propylthiouracil produced a decline in serum T3 plasma appearance rate T3 PAR (-55%; P < 0.02) in the T4-replaced lean rat but no alteration in T3 metabolism in the fatty Zucker rat. We conclude that the obese Zucker rat has impaired T3 synthesis in tissues containing Type I 5-deiodinase despite adequate T4 availability as substrate for deiodination to T3.

Maintenance of thyroid hormone production during exercise-induced weight loss.

Calorie restriction reduces thyroxine (T4) and 3,5,3'-triiodothyronine (T3) production, but the effects of exercise-induced weight loss on thyroid hormone metabolism in rodents are unclear. We studied the effects of chronic exercise on T4 and T3 metabolism comparing exercising (exercise) rats pair fed to sedentary (control) rodents and to weight-matched underfed sedentary animals (underfed; caloric intake 75% of ad libitum-fed controls). The exercise group utilized voluntary running wheels (28 days), and thyroid hormone metabolism was assessed using a three-compartment kinetics model. The exercise and underfed groups were equivalent in weight, but protein mass was greater in the exercise vs. underfed groups (30.4 +/- 0.5 vs. 27.9 +/- 0.5 g; P less than 0.05). During exercise, the T4 plasma clearance rate (PCR) was decreased (-39.2%; P less than 0.01) and the T4 concentration in serum was increased (48.6%; P less than 0.01), resulting in an unchanged T4 plasma appearance rate (PAR) vs. the control group. The decrease in T4 PCR in the exercise group was associated with a lower transport rate of T4 out of the slow pool (P less than 0.01). In the underfed group there was a reduction in both T4 serum concentration and PAR (-36%; P less than 0.01) compared with the control group, which was associated with a decrease in the volume of distribution (-25%; P less than 0.01). T3 PAR decreased 38.7% (P less than 0.01) during underfeeding but only 16.9% (P = not significant) during exercise vs. the control group.(ABSTRACT TRUNCATED AT 250 WORDS)