Influence of thyroid status on lipid metabolism in the perfused rat liver.

Thyroid disease is often accompanied by changes in the concentrations of serum lipids and lipoproteins. To evaluate the hepatic contribution to the serum abnormalities in thyroid disease, we examined fatty acid metabolism in perfused livers from pair-fed rats made hypothyroid with propylthiouracil (PTU) or made hyperthyroid by treatment with triiodothyronine (T(3)). The animals treated with T(3) became hyperphagic, depending on dose of drug and duration of hyperthyroidism. It was necessary, therefore, for appropriate controls, that food intake of T(3)-treated rats be restricted to quantities consumed by euthyroid rats. Animals treated with PTU for 2 wk became hypophagic, and therefore, food consumption of controls was restricted to that eaten by rats receiving PTU. Dependent on dose of T(3) and duration of treatment, the output of triglyceride and glucose was diminished, whereas output of ketone bodies was increased by livers from hyperthyroid animals. In contrast, livers from PTU-treated animals secreted increased amounts of triglyceride and glucose, whereas ketogenesis was diminished. The best models for study proved to be animals treated with either 10 mug T(3)/100 g body wt per d or 1 mg PTU/100 g body wt per d for 7 d. Under these conditions, all animals consumed the same quantity of food as did the euthyroid rats, but continued to display the metabolic alterations outlined above. The effects of PTU on hepatic metabolism were readily reversible by simultaneous administration of T(3). It is clear from these data that the thyroid status of the rat regulates hepatic triglyceride formation and secretion, and ketogenesis.