Very low-density lipoprotein metabolism in hypothyroid horses

The central hypothesis of this thesis is that hypothyroidism alters the metabolism of blood lipoproteins in horses. More specifically, our goal was to determine the effect of hypothyroidism on very low-density lipoprotein (VLDL) metabolism. Thyroid glands were surgically removed (thyroidectomy) from horses to create a hypothyroid state and blood lipids were examined. Results revealed a significant 9-fold rise in mean plasma VLDL concentration following thyroidectomy. Elevated lipoprotein concentrations were hypothesized to have resulted from altered VLDL metabolism. Kinetic parameters of apolipoprotein (apo) B metabolism were measured in a second group of thyroidectomized horses. Surprisingly, plasma VLDL concentrations were only 1.7-fold higher after thyroidectomy and hypothyroidism did not affect VLDL metabolism. In vivo kinetic parameters of VLDL apoB-48 metabolism were measured for the first time. Metabolism of apoB-48 VLDL differed significantly from that of apoB-100 VLDL. Discrepancies between plasma VLDL concentrations reported from these studies were hypothesized to have resulted from differences in feeding practices. Horses in the first study were deprived of feed overnight before collection of samples, and consumed a commercial feed containing 4% of digestible energy (DE) as fat. Plasma NEFA and VLDL concentrations significantly increased (9-fold and 7-fold, respectively) in horses deprived of feed for 96 hours, but hypothyroidism did not significantly affect results. Two isocaloric experimental feeds containing 2% and 6.6% of DE as fat were fed to euthyroid and hypothyroid horses. The plasma VLDL response to consumption of experimental feeds was affected by hypothyroidism, although differences did not reach statistical significance. Lower plasma concentrations of VLDL, measured as triglyceride-rich lipoprotein (TRL), were detected in euthyroid horses consuming experimental feeds. In contrast, higher plasma TRL concentrations were detected in hypothyroid horses fed the same diets. We conclude that hypothyroidism alters resting plasma VLDL concentrations in horses, but only small differences are observed. Thyroid hormone appears to be more important, however, at times when VLDL metabolism is challenged by consumption of high-fat or high-carbohydrate feeds. Results reveal that VLDL composition, plasma low-density lipoprotein concentrations, plasma lipase activity, and hepatic microsomal triglyceride transfer protein (MTP) expression are also affected by hypothyroidism