Thyroid hormone receptor subtype-β-selective agonists as potential treatments for metabolic syndrome

Thyroid hormones are of interest because of their ability to reduce serum cholesterol and triglycerides and their ability to reduce adiposity. Unfortunately, naturally occurring thyroid hormones, such as T3 (thyroid hormone) or T4 (thyroxine), cannot be used to treat obesity or hyperlipidemia in euthyroid subjects owing to cardiovascular complications. The two primary thyroid hormone receptor (TR) subtypes, TRα and TRβ, are ubiquitously expressed, with TRα predominance in heart, bone and brain and TRβ predominance in the liver and pituitary. This selective expression and perhaps selective TR function makes TRβ agonists potentially useful for treating obesity and hyperlipidemia without cardiac effects. TRβ-selective activation shows promise as there is a therapeutic window in which cholesterol is lowered and metabolic rate is increased without cardiac acceleration. This was shown in TRα-/- mice and for the TRβ-selective agonists GC-1 and KB-141. This should translate into antiobesity, lipid-lowering and po...