The time course of changes in lipid metabolism by dietary n-3 PUFAs (polyunsaturated fatty acids) in streptozotocin-induced diabetic rats during pregnancy (days 12 and 21) and their macrosomic offspring at birth (day 0) and through adulthood (days 60 and 90) was studied with respect to adipose tissue, liver and serum lipid concentrations, and fatty acid composition. Glucose and insulin levels were also assessed in order to characterize the diabetic state of macrosomic offspring. Pregnant diabetic and control rats were fed either an Isio-4 or EPAX diet (enriched with n-3 PUFA). The same diets were also consumed by pups at weaning. Compared with control rats, during pregnancy diabetic rats had a significant elevation in liver and serum triacylglycerol (triglyceride) and cholesterol concentrations. At birth, macrosomic pups had higher serum insulin and glucose levels than control pups. The macrosomic rats maintained accelerated postnatal growth combined with high adipose tissue weight and lipid content through the first 12 weeks of age. The macrosomic pups from diabetic rats fed the Isio-4 diet also showed a significant enhancement in liver and serum triacylglycerol and cholesterol levels at birth and during adulthood. Feeding the EPAX diet to diabetic mothers as well as their macrosomic pups increased serum and liver levels of EPA (eicospentaenoic acid) and DHA (docosahexaenoic acid) with a reduction in arachidonic acid. The EPAX diet induced a significant decrease in liver and serum triacylglycerol and cholesterol concentrations in mothers during pregnancy and in their macrosomic pups during adulthood. Since the EPAX diet improves lipid anomalies considerably in diabetic mothers and their macrosomic offspring, it may prevent long-term metabolic abnormalities associated with macrosomia.

GUERMOUCHE, BAYA, AKADIRI YESSOUFOU, NASSIMA SOULIMANE, HAFIDA MERZOUK, KABIROU MOUTAIROU, AZIZ HICHAMI, AND NAIM AKHTAR KHAN. n-3 fatty acids modulate T-cell calcium signaling in obese macrosomic rats. Obes Res. 2004;12: 1744 -1753. Objective: We investigated the effects of a diet containing EPAX-7010, rich in PUFAs such as eicosapentaenoic acid [20:5(n-3)] and docosahexaenoic acid [22:6(n-3)], i.e., a PUFA/EPAX regimen, on T-cell activation in diabetic pregnant rats and their obese pups. Research Methods and Procedures:Mild hyperglycemia in pregnant rats was induced by intraperitoneal injection of streptozotocin on Day 5 of gestation. T-cell blastogenesis was assayed by using 3 H-thymidine, whereas intracellular free calcium concentrations ([Ca 2ϩ ]i) were measured by using Fura-2 in diabetic pregnant rats and their obese offspring. Results: Concavalin-A-stimulated T-cell proliferation was decreased in both pregnant diabetic rats and their obese pups as compared with control animals. Feeding the PUFA/ EPAX diet restored T-cell proliferation in both groups of animals. We also employed ionomycin, which at 50 nM opens calcium channels, and thapsigargin (TG), which recruits [Ca 2ϩ ]i from endoplasmic reticulum pool. We observed that ionomycin-induced increases in [Ca 2ϩ ]i in Tcells of diabetic mothers and obese offspring were greater than in those of control rats. Furthermore, feeding PUFA/ EPAX diet diminished significantly the ionomycin-evoked rise in [Ca 2ϩ ]i in diabetic and obese animals. TG-induced increases in [Ca 2ϩ ]i in T-cells of diabetic pregnant rats and their obese offspring were greater than in those of control rats. The feeding of the experimental diet significantly curtailed the TG-evoked increases in [Ca 2ϩ ]i in both diabetic and obese rats. Discussion: Together, these observations provide evidence that T-cell activation and T-cell calcium signaling are altered during gestational diabetes and macrosomia. Hence, dietary fish oils, particularly eicosapentaenoic acid and docosahexaenoic acid, may restore these T-cell abnormalities.

In this work, we assessed the in-vitro effects of eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) (final concentration, 15 microM) on T cell blastogenesis, interleukin-2 and -4 (IL-2, IL-4) secretion, fatty acid composition and intracellular oxidative status in type I diabetic patients with or without complications. Con A stimulated lymphocyte proliferation, glucose uptake, intracellular reduced glutathione levels and catalase activity were lower in diabetics as compared to controls, regardless to the presence of complications. EPA and DHA diminished T-lymphocyte proliferation and IL-2 production but enhanced IL-4 secretion in both diabetic and control groups. No changes in the levels of reduced glutathione and in the activities of catalase and SOD were observed in control T cells cultured in the presence of EPA and DHA. However, in diabetic patients, addition of n-3 PUFA to culture induced an increase in T cell levels of reduced glutathione and hydroperoxide, and in activities of catalase and SOD. Low levels of arachidonic acid (C20:4n-6) were found in plasma membrane phospholipids of lymphocytes from diabetic patients compared to controls. Incubation of lymphocytes with EPA and DHA was associated with an incorporation of these fatty acids in membrane phospholipids. In conclusion, the beneficial effects of n-3 PUFA on T cell functions in type I diabetes could be attributed to their suppressive action and modulation of cytokine secretion, and to the improvement of intracellular oxidative status.

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