Increased intestinal phospholipase A(2) activity catalyzed by phospholipase B/lipase in WBN/Kob rats with pancreatic insufficiency

Male WBN/Rob rats derived from the Wistar strain spontaneously develop chro nic pancreatitis as late as 3 months old. To assess the degree of disease s everity, we compared the lipolytic enzyme levels in pancreas of 2-, 4-, and 6-month-old WBN/Kob rats fed isocaloric no fat (NF) and high fat (HF, 57% of total calories) diets and its pathology. Diet treatment did not signific antly affect lipase and group Ib phospholipase A(2) (PLA(2)) levels in the pancreas at all ages. Development of chronic pancreatitis at the age of 4 a nd 6 months was consistent with the tendency of decreasing group Ib PLA(2) specific content determined by enzyme immunoassay and lipase activity, and the decreased number of group Ib PLA(2)-positive acinar cells. Pancreatic l ipase and group Ib PLA(2) levels of 4-month-old WBN/Kob rats were significa ntly lower than those of control Wistar rats at age 4 months irrespective o f diet. This allowed us to adopt 4-month-old WBN/Kob rats as a model of pan creatic insufficiency, which could be a useful tool to examine the role of gastrointestinal enzymes in lipid digestion. Ca2+-independent PLA(2) activi ty of brush border membrane-associated phospholipase B/lipase (PLB/LIP) in ileal mucosa increased significantly in 4-month-old WBN/Kob rats while its content and transcript levels remained constant, suggesting its activation at the enzyme level. In WBN/Kob rats fed the HF diet at age 4 months, PLA(2 ) activity catalyzed by PLB/LIP in the proximal ileal mucosa was four times the total PLA(2) activity in the intestinal lumen. These results indicate that PLB/LIP compensates for the depletion of pancreatic lipolytic enzymes in WBN/Kob rats with pancreas insufficiency. (C) 2000 Elsevier Science B.V. All rights reserved.