Increased intestinal phospholipase A2 activity catalyzed by phospholipase B/lipase in WBN/Kob rats with pancreatic insufficiency

Male WBN/Kob rats derived from the Wistar strain spontaneously develop chronic pancreatitis as late as 3 months old. To assess the degree of disease severity, 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 significantly affect lipase and group Ib phospholipase A2 (PLA2) levels in the pancreas at all ages. Development of chronic pancreatitis at the age of 4 and 6 months was consistent with the tendency of decreasing group Ib PLA2 specific content determined by enzyme immunoassay and lipase activity, and the decreased number of group Ib PLA2-positive acinar cells. Pancreatic lipase and group Ib PLA2 levels of 4-month-old WBN/Kob rats were significantly lower than those of control Wistar rats at age 4 months irrespective of diet. This allowed us to adopt 4-month-old WBN/Kob rats as a model of pancreatic insufficiency, which could be a useful tool to examine the role of gastrointestinal enzymes in lipid digestion. Ca2+-independent PLA2 activity 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, PLA2 activity catalyzed by PLB/LIP in the proximal ileal mucosa was four times the total PLA2 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.