Research Article

Determination of T4-5’ deiodinase activity and metabolic sequelae in peripheral tissues of congenic lean and obese LA/Ntul//-cp rats

Abstract

Thyroid hormones are well established entities that readily mediate numerous essential biochemically-mediated elements of normal development, growth and energy metabolism (EM) expressed at the genomic level in response to alterations in diet and environment. A family of three highly specific Iodothyronine deiodinases consist of a subfamily of three deiodinase enzymes that exert important roles in the activation and deactivation of thyroid hormones in virtually all somatic tissues of vertebrate organisms. Thus, thyroid hormones can directly bring about genomic-mediated variations in gene expression and in the rate of metabolism including pathways of energy expenditure and in the conservation of energy utilization in peripheral tissues. Groups of lean and obese animals were subjected to measures of resting and norepinephrine stimulated VO2, measures of plasma insulin and glycemic parameters, tissue T3 and total in vitro deiodinase activity in multiple tissues, T4 half-life, and T3 nuclear hepatic receptor binding occupancy. The VO2 of resting and dose related NE stimulated VO2 of lean > obese, and serum and tissue T3 of lean > obese, and T4-5’ deiodinase activity of lean > obese in liver and obese > lean in IBAT. T3 receptor occupancy was decreased and T4 half-life was prolonged in the obese phenotype. These results indicate that net T4 activation to T3 and hepatic T3 nuclear receptor binding is decreased in the obese phenotype, and despite the increase in IBAT mass, the decreases in thyroidal actions and hyperinsulinemia are likely contributors to the decreased capacity for resting and NE-stimulated thermogenesis and contributors to greater adiposity in the obese phenotype of this strain.