Hypolipidemic and glycogenolytic effect of clofibrate (CPIB) in hypothyroid mice: role of insulin and glucagon.

1. The role of endogenous glucagon and insulin on the hypolipidemic and glycogenolytic effect of clofibrate was determined in the euthyroid and propylthiouracil (PTU)-induced hypothyroid mice. 2. PTU was fed in diet (0.15%) for 2 weeks and then clofibrate added to diet (0.25%) for 4 weeks. 3. Both PTU and clofibrate significantly increased liver weight but had no effect on kidney weight. PTU significantly decreased plasma triglycerides (TG) and increased cholesterol (Ch). 4. Clofibrate had a significant hypotriglyceridemic effect in both euthyroid and hypothyroid mice but did not affect plasma cholesterol. 5. Clofibrate decreased hepatic glycogen in euthyroid but not in hypothyroid mice. 6. Glucose-6-phosphatase activity was not affected by either PTU or clofibrate. 7. Neither PTU nor clofibrate affected hepatic TG or Ch. 8. Biliary lipid changes due to PTU treatment were reversed by clofibrate administration. 9. Since plasma insulin and glucagon levels were not affected by clofibrate in either euthyroid or hypothyroid mice, our results suggest that the hypotriglyceridemic and glycogenolytic effect of clofibrate is not mediated by changes in circulating insulin and glucagon ratio. 10. Moreover, while the glycogenolytic effect of clofibrate seems to be dependent, the hypotriglyceridemic effect seems to be independent of thyroid hormones.