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RESEARCH PRODUCT

n-3 Fatty Acids Modulate T-Cell Calcium Signaling in Obese Macrosomic Rats

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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 3H-thymidine, whereas intracellular free calcium concentrations ([Ca2+]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 [Ca2+]i from endoplasmic reticulum pool. We observed that ionomycin-induced increases in [Ca2+]i in T-cells 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 [Ca2+]i in diabetic and obese animals. TG-induced increases in [Ca2+]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 [Ca2+]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.