The effects of altered thyroid status on lipid metabolism in the genetic hyperlipemic Zucker rat

Exposure to thyroid hormone (T4) has been known to affect the plasma triglyceride (TG) as well as the plasma cholesterol level, but the mechanisms and degree of response in genetic hyperlipidemic states have not been defined. In the present study, we examined TG secretion and removal in vivo in genetically hyperlipemic Zucker rats maintained in hypothyroid, euthyroid, and hyperthyroid states for 6 weeks. The induction of the hypothyroid state resulted in marked weight loss with reduced food intake, and a parallel reduction in plasma TG concentration, hepatic TG production, and peripheral TG removal. In contrast, a similar degree of weight loss in the hyperthyroid state was associated with increased food intake, but no significant reduction in plasma TG concentration, production, or clearance. The changes in plasma cholesterol concentration in the hyperthyroid state were striking, with a 94% reduction in LDL cholesterol, but only a minimal reduction in the HDL cholesterol level. The hypercholesterolemic state in the Zucker rat. The results suggest that the very low density lipoprotein TG metabolism is influenced by hypothyroid but not the hyperthyroid state in this model of human genetic Type IV hyperlipemia. The primary reduction in LDL relative to HDL in response to thyroxine excess, suggests a therapeutic potential in disorders of genetic hyperlipidemia.