Effect of the obese phenotype on expression of hepatic T4–5’ deiodinase activity, T3 generation and thyroidal mediated actions in congenic LA/Ntul//–cprats

Abstract

Parameters of thyroidal responses to diet and environment have long been shown to be impaired in the obese phenotype of the LA/Ntul//–cp rat. To characterize the effect of expression of the obese phenotype on activity of maximum T4–5’ deiodinase (T4–DI) activity on adiposity and aspects of metabolism, groups of lean and obese littermates were subjected to measures of resting metabolic rate (RMR, VO2) at thermal neutrality (30°C) after a brief fast, followed by dose response Norepinephrine (NE) stimulation. Hepatic T4–DI activity represents a major source of hormonally active T3 in plasma and is readily delivered to peripheral tissues. At 16 weeks of age animals were sacrificed by cervical dislocation, blood was collected, and liver tissue was dissected for measures of serum levels of T3 and T4, and measures of maximal tissue dithiolthreitol (DTT)–stimulated T4–DI activity determined. The retroperitoneal and dorsal white adipose (WAT) depots were also dissected to estimate the magnitude of adiposity present upon sacrifice in each phenotype. Measures of RMR and the VO2 response to NE were greater in lean than obese phenotype, and indicators of BW and adiposity were much greater in obese than lean (p=<0.01). Measures of serum T3 were greater in lean than obese, but T4 was similar in both phenotypes. Measures of the rate of hepatic T4 DI activity were greater in lean than obese (p=<0.05), and the T1/2 for T4 disappearance were also prolonged in the obese phenotype. These results are consistent with other studies of impaired nonshivering thermogenesis in this strain, and suggest that decreased activity of hepatic T4–5’ deiodinase activity may be a contributing factor in the impaired capacity for nonshivering thermogenesis and excess fat accretion in the obese phenotype of this strain.