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.