Abstract
To determine the effects of aging and the obese phenotype on Triiodothyronine (T3) generation and thyroidal status, groups of congenic lean and obese female littermate LA/Ntul//-cp rats were maintained on Purina stock diet and house water from 4 until 24 months of age. Body weight and adiposity of obese >>> lean at all post weaning ages studied. Measures of resting oxygen consumption (RMR, VO2) at thermal neutrality (30°C), serum T3, T4, T4:T3 and T3:T4 ratios, tissue T3 concentrations, and T4-5’ deiodinase activity in liver, interscapular brown adipose tissue (IBAT), and gastrocnemius muscle (GNM) were determined at each age group. Measures of RMR were greater in lean than obese at each age (p=<0.05) and declined with age in both phenotypes with the most substantial decrease in the obese phenotype. Measures of serum T4 were greater at age 4 months than at both older ages measured in both phenotypes and remained similar thereafter. Serum T3 tended to increase modestly in each age in both phenotypes. Serum T4:T3 ratios decreased with age while serum T3:T4 ratios increased with age in both phenotypes. Measures of tissue T4-5’ Type II deiodinase activity were determined in isolated homogenates of liver, IBAT and GNM. Tissue activity levels of outer ring T4-5’ deiodinase activity of liver and IBAT showed both phenotype and age effects and decreased with age in both tissues. (Lean > obese; young > older) in both lean and obese phenotypes. GNM deiodinase activity increased only modestly with age in lean but not in obese rats. Liver T3 receptor affinity has also been reported to be decreased in the obese phenotype at 4 months of age. These observations are consistent with impaired sirtuin-mediated and age-associated thyroidal actions in the lean and obese phenotypes and which impairments may be contributory to further age associated decreases metabolic rates observed in the obese phenotype.
Published Version
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