Effect of phenotype on thyroidal parameters and metabolic sequelae in Wistar fatty rats

Abstract

To determine the effects of phenotype on parameters of peripheral thyroid hormone and actions, groups of adult male lean (LN) and obese (OB) Wistar Fatty Rats were fed a nutritionally adequate semisynthetic diet containing 54% carbohydrate, 16% mixed fats, 20% protein plus essential vitamins, minerals, and cellulose fiber for 8 weeks. Measures of weight gain (WG), feed efficiency ratio (FER), Resting (RMR) and norepinephrine (NE) stimulated VO2, serum triiodothyronine (T3), and in vitro T4-5’ deiodinase (5’DI) activity in liver (LVR), kidney (KID), gastrocnemius muscle (GNM) and interscapular brown adipose tissue (IBAT) were determined at baseline and after dithiothreitol (DTT) stimulation to optimize in vitro deiodination activity. The WG and FER of OB >> LN phenotype and FER increased over time in both phenotypes, with the greatest increase in the OB phenotype. The RMR of LN > OB, and NE-stimulation (200 µg/kg BW, sc) increased VO2 by 180% in LN but only ~30% in OB phenotype. Serum T3 of LN >> OB. Baseline 5’DI of OB > LN in LIV and KID and were of similar magnitude in both phenotypes in GNM and IBAT. After DTT stimulation, LIV increased ~200% in LN, ~30% in OB; In LN rats, KID +DTT increased ~200%, but only modest increases in OB phenotype, while in LN GNM, DTT resulted in 264% increase vs. +70% in OB rats. In IBAT, DTT resulted in ~ 30-fold increase in 5’DI in LN, and a 16-fold increase in 5’DI in the OB phenotype. These results indicate that parameters of thyroidal actions including circulating plasma levels of T3 and maximum capacity to generate T3 in peripheral tissues via 5’DI, although increased in the OB phenotype, were associated with decreases in RMR and NE-stimulated VO2. These observations occurred in association with an improved efficiency of FER and weight gain and dysregulation of intracellular T3 actions including parameters of T3 receptor affinity kinetics are likely to be among key contributors to the epigenetic expression of the OB+NIDDM phenotype in this strain and are consistent with a reduced affinity of T3- mediated cellular components of intermediary metabolism.