Determinants of human adipose tissue lipoprotein lipase. Effect of diabetes and obesity on basal- and diet-induced activity.

The role of insulin in the regulation of human adipose tissue lipoprotein lipase was evaluated. Adipose tissue heparin-releasable lipoprotein lipase (thought to be related to peripheral clearance of plasma triglycerides) was low in insulin-deficient, untreated hyperglycemic diabetic subjects (P less than 0.001) and treatment of hyperglycemia returned the activity to normal. In chronic hyperinsulinism, represented by obesity, heparin-releasable activity among control subjects was correlated to percent of ideal body weight (r=0.53, P less than 0.05) and to fat cell size (r=0.61, P less than 0.02). Acetone-ether powder lipoprotein lipase activity (presumed to reflect total tissue enzyme) was also related to percent of ideal body weight (r=0.76, P less than 0.001 for controls; r=0.67, P less than 0.05 for diabetics) and to fat cell size (r=0.71, P less than 0.01 for controls; r=0.85, P less than 0.01 for diabetics. Postprandial-stimulated insulin secretion was related to diet-induced changes in lipoprotein lipase in control subjects; both were dependent upon the amount of dietary carbohydrate. In contrast, the diabetic patients with low insulin responses, failed to increase lipoprotein lipase activity with feeding. The changes in heparin-releasable (r=0.66, P less than 0.01) and acetone-ether powder (r=0.69, P less than 0.01) activity during feeding were related to the percent increase in plasma insulin. Thus, insulin appears to be important in the regulation of human adipose tissue lipoprotein lipase activity. Elevated insulin levels in obesity and increased insulin secretion after eating were associated with increased lipoprotein lipase activity. Defects in insulin secretion, both in postabsorptive and postprandial states, are associated with low adipose tissue lipoprotein lipase and may lead to hypertriglyceridemia in diabetic man.

Effect of estrogen on post-heparin lipolytic activity. Selective decline in hepatic triglyceride lipase.

The rise in plasma triglyceride (TG) levels associated with estrogen administration has been thought to arise from impaired clearance because of the uniform suppression of post-heparin lipolytic activity (PHLA). Recently PHLA has been shown to consist of two activities: hepatic TG lipase and extrahepatic lipoprotein lipase (LPL). To determine whether estrogen might induce a selective decline in one of these activities, both hepatic TG lipase and extrahepatic LPL were measured in post-heparin plasma from 13 normal women before and after 2 wk of treatment with ethinyl estradiol (1 mug/kg per day). Hepatic TG lipase and extrahepatic LPL were determined by two techniques: (a) separation by heparin-Sepharose column chromatography, and (b) selective inhibition with specific antibodies to post-heparin hepatic TG lipase and milk LPL. Estrogen uniformly depressed hepatic TG lipase as measured by affinity column (-68 +/- 12%, mean +/- SD, P less than 0.001) or antibody inhibition (-63 +/- 11%, P less than 0.001). Extrahepatic LPL was not significantly changed by affinity column (-22 +/- 40%) or antibody inhibition (-3 +/- 42%). Direct measurement of adipose tissue LPL from buttock fat biopsies also showed no systematic change in the activated form of LPL measured as heparin-elutable LPL (+64 +/- 164%) or in the tissue form of LPL measured in extracts of acetone-ether powders (+21 +/- 77%). The change in hepatic TG lipase correlated with the change in PHLA (r = 0.969, P less than 0.01). However, neither the change in PHLA nor hepatic TG lipase correlated with the increase in TG during estrogen. The decrease in PHLA during estrogen thus results from a selective decline in hepatic TG lipase.

Glucocorticoids and triglyceride transport: effects on triglyceride secretion rates, lipoprotein lipase, and plasma lipoproteins in the rat.

In order to elucidate the mechanism(s) of hyperlipidemia following glucocorticoid administration, dexamethasone (0.125 mg/Kg) was administered daily intramuscularly for 2 wk to male Sprague-Dawley rats and the effects on plasma triglyceride (TG) and cholesterol (Chol), lipoprotein neutral lipids, hepatic triglyceride secretion rates (TGSR; Triton), and epididymal fat lipoprotein lipase (LPL) were determined. Special measures were taken to maintain positive caloric balance and keep the weights of control and dexamethasone-treated animals comparable. Significant increases (p less than 0.001) in TG and very-low density lipoprotein (VLDL) triglyceride associated with no change in Chol and actual reduction in both triglyceride and cholesterol in low density lipoprotein (ldl) were observed in the steroid-treated animals. Dexamethasone treatment was associated with increased basal insulin and glucose levels, an insignificant increment in TGSR, and a highly significant reduction (p less than 0.001) in LPL. These findings suggest that glucocorticoid treatment increases splanchnic triglyceride production rates, but the resulting hypertriglyceridemia is primarily a consequence of impaired VLDL removal due to low adipose tissue LPL activity.

Parathyroid hormone and triglyceride transport: effects on triglyceride secretion rates and adipose tissue lipoprotein lipase in the rat.

In order to determine the effects of parathyroid hormone on triglyceride transport, male Sprague-Dawley rats were injected with parathyroid extract for eight days and triglyceride secretion rates (TGSR) and adipose tissue lipoprotein lipase (LPL) activity were determined. Parathyroid hormone-treated rats demonstrated significantly lower (p less than .005) TGSR in the basal overnight fasted state 15 hours after the previous injection, but this effect on TGSR was not apparent 3 hours after PTE injection when the rats were allowed to eat. In contrast, LPL activity was significantly reduced in the PTH-treated animals at 3 hours and no effect was apparent on this index of triglyceride removal at 15 hours. These findings suggest that parathyroid hormone may exert independent influences on triglyceride production and removal and thus may alter triglyceride homeostasis in conditions in which parathyroid hormone levels are abnormally increased.