DIETARY OMEGA-3-FATTY-ACIDS AND CHOLESTEROL MODIFY ENTEROCYTE MICROSOMAL MEMBRANE PHOSPHIOLIPIDS, CHOLESTEROL CONTENT AND PHOSPHOLIPID ENZYME-ACTIVITIES IN DIABETIC RATS

Diabetes-associated changes in intestinal uptake of nutrients are modi fied by isocaloric variations in the type of dietary lipids, and are a ssociated with alterations in the phospholipid and fatty acyl content of the intestinal brush border membrane. The present study was designe d to test the hypothesis that diet- and diabetes associated changes in enterocyte microsomal membrane phospholipids are due to variations in the activity of two phospholipid metabolizing enzymes, 1,2-diacylglyc erol:CDP choline cholinephosphotransferase (CPT) and phosphatidylethan olamine methyltransferase (PEMT). Adult female Wistar rats were fed on e of four semisynthetic diets-beef tallow low in cholesterol (ET), bee f tallow high in cholesterol (BTC), fish oil low in cholesterol (FO) o r fish oil high in cholesterol. In half of the animals, diabetes melli tus was produced by injection of streptozotocin. Jejunal and ileal ent erocyte microsomes (EMM) were isolated and analyzed for cholesterol an d phospholipids, as well as for CPT and PEMT activities. In control an imals, feeding FO reduced EMM total phospholipids including phosphatid ylcholine (PC), phosphatidylethanolamine (PE) and phosphatidylinositol . Feeding FO resulted in a greater than 95% reduction in the activity of CPT. Diabetes was associated with increased jejunal EMM total phosp holipids including sphingomyelin (SM) and PE, without associated chang es in CPT or PEMT. Dietary cholesterol supplementation did not affect EMM total cholesterol or phospholipid composition in control rats fed BT or FO, but was associated with an increase in EMM cholesterol in di abetic rats fed BT or FO. A decrease in total phospholipids due to a d ecline in SM, PC and PE in diabetic rats fed FO was not associated wit h changes in the activities of CPT or PEMT in EMM. Thus (i) enterocyte microsomal membrane cholesterol and phospholipid contents are influen ced by diabetes, dietary cholesterol and the type of fatty acid in the diet, and (ii) changes in phospholipid composition are not fully expl ained by alterations in the activities of CPT and PEMT.