441 Effect of Dietary Fat on Diabetes-Induced Changes in Liver Microsomal Fatty Acid Composition and Glucose-6-Phosphatase Activity in Rats J.T. Venkatraman a,b,1 , D. Pehowich a,b, B. Singh c, R.V. Rajotte d, A.B.R. Thomson a,e, and M.T. Clandinina, b,e, * aNutrition and Metabolism Research Group, Departments of bFoods & Nutrition, Clmmunology, dSurgery and eMedicine, Universityof Alberta, Edmonton, Alberta, Canada T6G 2C2 Experimental diabetes may manifest itself in a defect in liver microsomal fatty acid desaturation and in- creased activity of glucose-6-phosphatase (G-6-Pase). The present study was designed to determine whether these changes could be normalized by a change in the dietary fat consumed. Control and streptozotocin- induced diabetic rats were fed nutritionally adequate diets which varied in fatty acid composition. Fatty acid analysis of liver microsomal phospholipids revealed that non-diabetic control animals fed saturated fat (beef tallow) or a diet high in oJ3 fatty acids (fish oil) exhibited a significantly higher level of 18:2~6 and a lower level of 20:4w6 in the phosphatidylcholine and phosphatidylethanolamine fractions compared with diabetic animals. Control and diabetic animals fed the high linoleic acid diet had similar levels of 18:2o~6 in the microsomal phosphatidylcholine and phosphati- dylserine fractions. Microsomal G-6-Pase activity was higher in diabetic than in control animals. Activity of G-6-Pase was lower in microsomes of control animals fed the soybean oil or the fish oil diet, but was not significantly reduced in diabetic animals fed high polyunsaturated fats. Blood glucose levels were sim- ilar in control groups fed the different diets, but the plasma hemoglobin Alc level was lower in diabetic animals fed the soybean oil diet. Cholesterol and triglyceride levels were lower in diabetic animals fed the fish oil-based diet. The results suggest that die- tary fat manipulation has the potential to change at least some of the abnormalities in the microsomal membrane in experimental diabetes. Lipids 26, 441-444 (1991). A defect in fatty acid desaturation is one of the complica- tions associated with experimental diabetes (1-4). As diabetes causes alterations in lipid composition and in the physical state of liver microsomal membranes (5,6), these changes may also affect microsomal membrane- bound enzymes. Microsomal glucose-6-phosphatase (G- 6-Pase), which plays a key role in dephosphorylation and transport of liver glucose into the blood (7), was reported to increase in the diabetic state (8). Abnormalities in lipoprotein metabolism have also been described in patients with non-insulin-dependent diabetes mellitus (9). Dietary polyunsaturated fatty acids may alter lipo- protein metabolism and are generally associated with a 1Present address: Division of Clinical Immunology, Department of Medicine, The University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78284. *To whom all correspondence should be addressed. Abbreviations: G-6-Pase, glucose-6-phosphatase; HgAlc, hemoglo- bin Alc. cholesterol-lowering effect and altered membrane lipid composition (10,11). The present study was designed to determine whether saturated to6 or to3 fatty acids nor- malize the changes that occur in microsomal membrane phospholipid fatty acid composition, plasma lipids, glu- cose and glucose-6-phosphatase activity in the experi- mental diabetes. MATERIALS AND METHODS Three semipurified diets containing 20% w/w fat were fed to rats. All diets were nutritionally adequate and differed only in fatty acid composition (Table 1). The beef tallow diet was based on a blend of beef tallow (18%), safflower oil (1%) and soybean oil (1%). The high linoleic acid diet contained 20% soybean oil. The fish oil diet consisted of a blend of 10% fish oil concentrate, 8% beef tallow and 2% safflower oil. Male Wistar-Furth strain rats, weighing 230-250 g, were placed in individual metabolic cages and monitored weekly for plasma glucose, urine volume, urine glucose, food consumption and body weight. Animals were ren- dered diabetic using 55 mg/kg streptozotocin (a gift from the Upjohn Company, Kalamazoo, MI) which was injected intravenously via the penile vein using citrate buffer (pH 4.5). Following induction of diabetes, the animals were TABLE 1 Composition of Experimental Diets Beef tallow Soybean oil Fish oil diet diet diet (g/kg Diet) Casein 270 270 270 Starch 200 200 200 Glucose 207.7 207.7 207.7 Cellulose 50 50 50 Vitamin mix~ l0 t0 10 Mineral mixb 50.85 50.85 50.85 Choline chloride 2.75 2.75 2.75 Inositol 6.25 6.25 6.25 L-Methionine 2.5 2.5 2.5 Soybean oil 10 200 -- Hydrogenated beef tallow 190 -- 80 Safflower oil 10 -- 20 Fish oil -- -- 100 aAOAC vitamin mix (Teklad test diets, Madison, WI) provided the following per kg of complete diet: 20,000 IU vitamin A; 2,000 IU vitamin D; 100 mg vitamin E; 5 mg menadione; 5mg thiamin-HC1; 8 mg riboflavin; 40 mg pyridoxine-HC1; 40 mg niacin; 40 mg panto- thenic acid; 2,000 mg choline; 100 mg myothiositol; 100 mg p- aminobenzoicacid; 0.4 mg biotin; 2 mg folic acid; and 30 mg vitamin B-12. aBerrhart Tomarelli mineral mix (General Biochemicals, Chagrin Falls, OH). LIPIDS, Vol. 26, No. 6 ('1991)