Pancreatic lipase (PL) and its related protein 1 (PLRP1) are regulated by the amount of dietary fat through an apparent transcriptional mechanism. Regulation of PL and PLRP1 by type of fat (chain length and degree of saturation) is less well understood. The aim of this study was to determine whether mediumchain triglycerides regulate PL and PLRP1. For 7 d, weanling (21-d-old) Sprague Dawley male rats were fed diets low (11% of energy), moderate (40% of energy), or high (67% of energy) in trioctanoate/tridecanoate (MCT) or safflower (low fat only) oils. Food consumption decreased as dietary MCT increased, and the consumption of MCT diets was lower than that of the lowsafflower (control) diet. Final body weight was similar among rats fed the low-or moderate-MCT or control diets, but was significantly reduced (17%) in those fed the high-MCT diets. PL activity was significantly elevated 53-60% (p Ͻ 0.002) in rats fed low and moderate MCT diets, respectively, compared with that of rats fed high-MCT or control diets. PL and PLRP1 mRNA levels were not significantly different among diets, suggesting that chain length regulates PL and PLRP1 translationally or posttranslationally. The -hydroxybutyrate plasma concentration was significantly (p Ͻ 0.02) higher (85%) in rats consuming low-MCT diet compared with those of rats fed the control diet. MCT at low levels, but not high levels, increase PL activity without changing its mRNA levels. Pancreatic lipase (PL) is the main enzyme responsible for digestion of dietary triglycerides. PL catalyzes the hydrolysis of 56% of the fatty acids of dietary triglycerides, and gastric lipase, an additional 10% (1). PL and its related protein PLRP1, a homologous protein of unknown function (2), are secreted by the pancreas and regulated by dietary fat (3-5). Considerable amount of work has been reported about the dietary regulation of PL by triglycerides, but many of the studies before 1994 used a cDNA probe initially believed to be PL and subsequently shown to be PLRP1 (2). PL was initially cloned by Lowe and co-workers (6) and referred to as rat PL3 by Wicker-Planquart and Puigserver (7). PL demonstrates the classical dependence on colipase for its lipolytic activity. PLRP1 (known before 1994 as pancreatic lipase 1/2) is highly homologous to PL (65%) (2, 8), but to date no known lipolytic activity of PLRP1 has been reported. Site-directed mutagenesis of two amino acids in PLRP1 to those seen in PL restores full colipase-dependent lipolytic activity of PLRP1, suggesting that PLRP1 may be a nonfunctional homologue of PL (9). Another homologue, pancreatic lipase related protein 2 (PLRP2) has 65% identity to PL and hydrolyzes triglycerides, phospholipids, and galactolipids. PLRP2 has low colipase dependence and does not exhibit bile salt inhibition as PL does (2,8,10,11). It is unknown whether PLRP2 is regulated by dietary fat.The pancreas normally produces and secretes 3-to 10-fold excess lipase; therefore, the physiologic importance of regulating PL has been questioned. However, the dieta...