Increased intestinal phospholipase A_2 activity catalyzed by phospholipase B/lipase in WNB/Kob rats with pancreatic insufficiency

摘要

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 A_2 (PLA_2) 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 PLA_2 specific content determined by enzyme immunoassay and lipase activity, and the decreased number of group Ib PLA_2-positive acinar cells. Pancreatic lipase and group Ib PLA_2 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. Ca~(2+)-independent PLA_2 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, 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.