Differential effects of n-3 polyunsaturated fatty acids on metabolic control and vascular reactivity in the type 2 diabetic ob/ob mouse.
ABSTRACT Diets rich in monounsaturated fatty acids (MUFA) are recommended for individuals with type 2 diabetes mellitus (T2DM). The American Heart Association recommends increasing intakes of n-3 polyunsaturated fatty acids (PUFA) to reduce the risk of vascular disease in high-risk individuals; however, the long-term effects of these bioactive fatty acids on glucose metabolism in insulin resistance are controversial. The present studies were conducted to evaluate the effects of diets rich in both MUFA and alpha linolenic acid (C18:3n-3, ALA), eicosapentaenoic acid (C20:5n-3, EPA), or docosahexaenoic acid (C22:6n-3, DHA), on glycemic control and other parameters related to vascular health in a mouse model of T2DM and insulin resistance. Male ob/ob mice (n = 15 per treatment) were fed 1 of 4 lipid-modified formula diets (LFDs) for 4 weeks: (1) MUFA control, (2) ALA blend, (3) EPA blend, and (4) DHA blend. A portion of a MUFA-rich lipid blend in the control LFD was replaced with 11% to 14% energy as n-3 PUFA. After 4 weeks, plasma glucose response to a standard meal (1.5 g carbohydrate/kg body weight) and insulin challenge (2 U/kg body weight, IP) was assessed, and samples were collected for analysis of glucose, insulin, and lipids. Vascular reactivity of isolated aortic rings was assessed in an identical follow-up study. The results showed that insulin-resistant mice fed an LFD with EPA and/or DHA blends had significantly (P < .05) lower triglycerides and free fatty acids, but insulin sensitivity and fasting plasma glucose were not improved. However, mice fed with the ALA blend had significantly improved insulin sensitivity when compared to those fed with other LFD (P < .05). Animals fed an LFD with n-3 PUFA from marine or plant sources showed significantly improved vascular responses as compared with the MUFA-rich LFD (E(max), P < .05) and ob/ob reference mice consuming chow (E(max) and pEC(50), P < .05). In summary, long-term consumption of LFD with n-3 PUFAs improved blood lipids and vascular function in an animal model of insulin resistance and T2DM; however, only MUFA-rich LFD with ALA also improved both insulin sensitivity and glycemic responses. Further studies of MUFA-rich LFD with ALA with individuals who have T2DM are warranted.
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ABSTRACT: The consumption of diets enriched in monounsaturated fat has been related to a lower rate of coronary heart disease. It is well known that this dietary model decreases LDL-cholesterol plasma levels when replacing a saturated fat enriched diet. For this reason, a high monounsaturated fat diet is now being advocated to prevent cardiovascular disease, especially in Mediterranean countries. However, some expert panels-the Joint Task Force of European and other Societies on Coronary Prevention and the International Task Force for Prevention of Coronary Heart Disease-recommend replacing dietary saturated fat by complex carbohydrates, limiting the intake of total fat to <30% of the energy and monounsaturated fat to no more than 10-15% of total calories, reaching a similar effect on LDL-cholesterol plasma levels to a high monounsaturated fat diet. The most appropriate nutritional model to prevent arteriosclerosis should be supported by research into other biological effects of both diets. Therefore, it is interesting to review the non-lipid effect of monounsaturated fat, starting with its influence on other cardiovascular risk factors, such as carbohydrate metabolism and blood pressure. Moreover, substantial evidence of the effect of dietary monounsaturated fat on a wide range of healthy benefits beyond cholesterol, which have been investigated in recent years, such as lipoprotein oxidation, coagulation, fibrinolysis and endothelium, will be discussed. Furthermore, many observational epidemiological studies suggest that a high intake of monounsaturated fat is associated with reduced coronary risk and this will be analyzed in accordance with the clinical evidence to discuss the best dietary model to prevent coronary artery disease.Atherosclerosis 09/2002; 163(2):385-98. · 3.71 Impact Factor
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ABSTRACT: Acute elevations of plasma free fatty acid (FFA) levels augment glucose-stimulated insulin secretion (GSIS). Prolonged elevations of FFA levels reportedly impair GSIS, but no one has previously compared GSIS after prolonged exposure to saturated or unsaturated fat. Rats received a low-fat diet (Low-Fat) or one enriched with either saturated (Lard) or unsaturated fat (Soy) for 4 weeks. Insulin responses during hyperglycemic clamps were augmented by saturated but not unsaturated fat (580 +/- 25, 325 +/- 30, and 380 +/- 50 pmol x l(-1) x min(-1) in Lard, Soy, and Low-Fat groups, respectively). Despite hyperinsulinemia, the amount of glucose infused was lower in the Lard compared with the Low-Fat group. Separate studies measured GSIS from the perfused pancreas. Without fatty acids in the perfusate, insulin output in the Lard group (135 +/- 22 ng/30 min) matched that of Low-Fat rats (115 +/- 13 ng/30 min), but exceeded that of Soy rats (80 +/- 7 ng/30 min). When FFAs in the perfusate mimicked the quantity and composition of plasma FFAs in intact animals, in vivo insulin secretory patterns were restored. Because the GSIS of rats consuming Lard diets consistently exceeded that of the Soy group, we also assessed responses after 48-h infusions of lard or soy oil. Again, lard oil exhibited greater insulinotropic potency. These data indicate that prolonged exposure to saturated fat enhances GSIS (but this does not entirely compensate for insulin resistance), whereas unsaturated fat, given in the diet or by infusion, impairs GSIS. Inferences regarding the impact of fatty acids on GSIS that are based on models using unsaturated fat may not reflect the effects of saturated fat.Diabetes 07/2002; 51(6):1825-33. · 7.90 Impact Factor
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ABSTRACT: Summary This study was conducted to examine the effect of ω3 fatty acid supplementation on plasma lipid, cholesterol and lipoprotein fatty acid content of non-insulin-dependent diabetic individuals consuming a higher (0.65, n = 10) or lower (0.44, n = 18) ratio of dietary polyunsaturated to saturated fatty acid (P/S). The participants were initially given an olive oil supplement (placebo) equivalent to 35 mg of 18:1 · kg body weight–1· day–1 for 3 months. This was followed by two ω3 supplement periods in a randomized crossover. In these 3-month periods, participants were given a linseed oil supplement equivalent to 35 mg of 18:3ω3 · kg body weight–1· day–1 or a fish oil supplement equivalent to 35 mg of 20:5ω3 + 22:6ω3 · kg body weight–1· day–1. At the end of each supplement period, a blood sample was drawn from each participant for lipid, lipoprotein, insulin, glucagon and C-peptide analyses. At the end of each 3-month period a 7-day dietary record was completed to calculate dietary fat intake and P/S ratio. Results indicate that fish oil significantly reduced plasma triacylglycerol level (p < 0.05) and increased 20:5ω3 and 22:6ω3 content of all lipoprotein lipid classes. Linolenic acid supplementation had no effect on plasma triacylglycerol level, but it increased 18:3ω3 content of lipoprotein cholesterol ester fractions (p < 0.05). A slight increase in 20:5ω3, but not 22:6ω3, content was noted in lipoprotein lipid classes as a result of 18:3ω3 supplementation. LDL and HDL cholesterol, insulin, glucagon and C-peptide levels were not affected by either ω3 supplement. It is concluded that a modest intake of ω3 fatty acids, such as could be obtained from consuming fish regularly, will reduce plasma triglyceride level without affecting LDL or HDL cholesterol levels. [Diabetologia (1997) 40: 45–52]Diabetologia 01/1997; 40(1):45-52. · 6.49 Impact Factor