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

Abstract

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.

Docosahexaenoic acid reduces suppressive and migratory functions of CD4CD25 regulatory T-cells

“…Hence, we can state that DHA infl uences the Treg cell activity by being incorporated into their plasma membranes. Our observations corroborate our previous fi ndings ( 43,46 ), wherein we have shown that dietary n-3 PUFA were significantly incorporated into the plasma membranes and, consequently, modulate T-cell activation. However, the mechanism of action of in vivo PUFA enrichment of T-cell phospholipids can be explained on the basis of the reports that have shown that incubation of T-cells with PUFA leads to the displacement of Src family protein tyrosine kinase from lipid rafts in parallel with the inhibition of calcium response ( 47,48 ).…”

N-3 Fatty acids modulate antioxidant status in diabetic rats and their macrosomic offspring

“…Total oil comprised 5% of the diet. [17][18][19][20][21] In the EPAX diet, half of the vegetable oil Isio-4 was replaced by EPAX-7010. The composition of the mineral and the vitamin mix was identical to that described by Triboulot et al 17 Isio-4 oil contained in mg/g, 47.2, 18 : 2 (n-6), 1.7, total (n-3) and 40.2, monounsaturated fatty acids (largely 18 : 1).…”

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

“…[18][19][20] Other researchers have reported that feeding a diet enriched in EPA and DHA to macrosomic pups of diabetic dams improved the proliferative response of splenocytes to concanavalin A (ConA) and lowered the Th1:Th2 of serum cytokines. 21,22 These studies suggest that feeding fish oil (FO) to obese rodents may lower the inflammatory reaction and improve T-cell proliferative responses in the spleen. Hence, the objectives of this study were to determine the influence of obesity on MLN immune cell function and to establish if a diet supplemented with long-chain (n-3) PUFA could improve the immune dysfunction present in the gut-associated lymph nodes in the obese JCR:LA-cp rat through modifications to the membrane fatty acid composition of MLN immune cells.…”