Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: Selective actions relative to 3,5,3′-triiodo-L-thyronine

Current drug therapies for obesity are ineffective, and existing treatments for lipid disorders can be further improved. Thyroid hormones affect both conditions, although currently available nonselective thyromimetics are not clinically useful for such treatment due to cardiac side effects. Recent studies suggest that thyroid hormone receptor subtype β (TRβ) selective agonists have a profile in which cholesterol can be reduced with minimal tachycardia. The purpose of this study was to determine whether modest (5–10%) increases in metabolic rate could also be observed with minimal tachycardia after TRβ stimulation. For these studies, the TRβ selective agonist, GC-1, was used to assess selectivity for lipid-lowering and metabolic rate changes relative to tachycardia. Studies in cholesterol-fed rats (7 d treatment) showed that GC-1 reduced cholesterol (ED50 = 190 nmol/kg·d) approximately 30 times more potently than it induced tachycardia (ED15 = 5451 nmol/kg·d). T3 showed no potency difference between choles...