RELATIONSHIP BETWEEN IMPROVED POSTPRANDIAL LIPEMIA AND LOW-DENSITY-LIPOPROTEIN METABOLISM DURING TREATMENT WITH TETRAHYDROLIPSTATIN, A PANCREATIC LIPASE INHIBITOR

The effect of tetrahydrolipstatin (THL), a recently developed pancreatic lipase inhibitor, on fasting plasma lipid levels and postprandial lipoprotein and retinyl palmitate (RP) metabolism was studied in 17 hyperlipidemic subjects, using an oral RP fat load (8 hours, 50 g fat/m2). During therapy with THL, fasting plasma cholesterol, low-density lipoprotein (LDL) cholesterol, and apolipoprotein (apo) B concentrations decreased by 8% (P = .006), 9% (P = .002), and 10% (P = .002), respectively. The postprandial plasma triglyceridemia, which was expressed as the area under the 8-hour triglyceride (TG) curve, improved by 27% during THL therapy (P = .04) without changes in fasting plasma TG or high-density lipoprotein (HDL) cholesterol levels. The improved postprandial triglyceridemia was accompanied by a 19% reduction in circulating levels of chylomicrons and chylomicron remnants, determined by the decreased areas under the 8-hour RP curves. The most likely mechanisms involved are decreased formation of chylomicrons by a decrease of intestinal TG absorption as a consequence of THL treatment, as well as reduced delivery of dietary lipid and fatty acids to the liver and subsequent upregulation of hepatic LDL receptors. In agreement with the latter mechanism, the decrease in postprandial lipemia expressed as δ area under the TG curve was significantly related to the decrease (δ) in LDL cholesterol level during THL treatment (r = .81, P = .0001). The present data indicated that pancreatic lipase inhibition improved postprandial lipoprotein metabolism, which in turn resulted in lower plasma total and LDL cholesterol concentrations. © 1994.