Decreased Neonatal Dietary Fat Absorption and T Cell Cytotoxicity in Pancreatic Lipase-related Protein 2-Deficient Mice

Abstract

The pancreas secretes several different lipases. The most abundant is pancreatic triglyceride lipase (PTL). The pancreas also synthesizes two homologues of PTL, the pancreatic lipase-related proteins 1 and 2 (PLRP1 and PLRP2). Cytotoxic T-lymphocytes also express PLRP2 under certain conditions. We sought to determine the role of PLRP2 in fat absorption and in T-cell cytotoxicity by creating a PLRP2-deficient mouse. Adult PLRP2-deficient mice had normal fat absorption. In contrast, suckling PLRP2-deficient mice had fat malabsorption evidenced by increased fecal weight, increased fecal fats, and the presence of undigested and partially digested dietary triglycerides in the feces. As a result, the PLRP2-deficient pups had a decreased rate of weight gain. To assess T cell cytotoxicity, we immunized PLRP2-deficient mice with a mastocytoma cell line, P815, and determined the ability of splenocytes from the immunized mice to kill P815 cells in a 51 Cr release assay. PLRP2-deficient cells had deficient killing activity in this assay, and PLRP2-deficient splenocytes released fewer fatty acid from the target cells than did control cells. Our results provide the first evidence of a physiological function for PLRP2. PLRP2 participates in T cell cytotoxicity, and PLRP2 performs a crucial role in the digestion of dietary fats in suckling animals.

Effect of Long-term High-Fat Feeding on the Expression of Pancreatic Lipases and Adipose Tissue Uncoupling Proteins in Mice

“…The probes for UCP1 and UCP2 as well as for mouse pancreatic lipase, PLRP1, and PLRP2 have been described previously (14,19). The 18S rRNA probe was purchased from DNA Technology (Denmark).…”

“…Rat PLRP2, first identified as a zymogen granule membrane protein, GP-3, is a pancreatic lipase with kinetic properties that differs from traditional pancreatic lipase (13). PLRP2 has broader substrate specificity than pancreatic lipase and is not colipase-dependent (14). No lipase activity has been detected for PLRP1; however, it binds colipase with an affinity equal to that of lipase.…”

“…No lipase activity has been detected for PLRP1; however, it binds colipase with an affinity equal to that of lipase. Its structural properties suggest that PLRP1 may participate in dietary fat metabolism (14); however, its physiological action is still unknown. Both PLRP1 and PLRP2 are expressed during early gestation and increase to maximum levels at 12 hours after birth, thereafter declining with age (15).…”

“…Both PLRP1 and PLRP2 are expressed during early gestation and increase to maximum levels at 12 hours after birth, thereafter declining with age (15). PLRP2 has been shown to be important for fat digestion in the neonate (14).…”

Genes involved in obesity: Adipocytes, brain and microflora

“…Other host molecules, such as mucins and glycosphingolipids, can also be degraded by bacterial enzymes (Lowe et al, 1998). Altogether, by serving as nutrient sources, these microbe-degraded host glycans establish a mutually beneficial host-bacterial interaction.…”