γ-Linolenic Acid Restores Renal Medullary Thick Ascending Limb Na+,K+-ATPase Activity in Diabetic Rats

In diabetes, the activity of -6 desaturase, which converts linoleic acid (LA) into -linolenic acid (GLA), the first step of arachidonic acid (AA) synthesis, is decreased, leading to alterations in membrane phos- pholipid composition. On the other hand, 12 wk after the onset of diabetes, Na,K-ATPase activity is reduced in many organs, including the kidney. The medullary thick ascending limb (MTAL) reduced Na,K-ATPase activity, whereas the sodium load secondary to glomerular hyperfiltration was increased. The aim of our study was to examine whether the changes in membrane fatty acid composition resulting from the inhibition of -6 desaturase may be involved in the decreased Na,K-ATPase activity observed in the outer MTAL after 12 wk of diabetes. GLA is a fatty acid that by-passes the -6 desaturase step. We measured the membrane fatty acid composition and the Na,K-ATPase activity in the renal outer medulla of control and streptozotocin (STZ)-induced diabetic rats 12 wk after the induction of diabetes. Measurements were performed after supplementation of control rats with sunflower oil (SO) or GLA for 12 wk, and supplementation of 12 wk diabetic rats with SO for 12 wk or with GLA for 6 or 12 wk. Supplementation with GLA not only prevented the decrease in Na,K-ATPase activity observed after 12 wk of diabetes but also time dependently stimulated Na,K-ATPase activity in the outer medulla. The changes in Na,K-ATPase activity were related to parallel changes in the amount of Na,K-ATPase 1 subunit protein. In addition, in diabetic rats only, Na,K-ATPase activity was positively correlated with the amount of AA present in cell membranes (r 0.92, P 0.05). Our results indicate that nutritional GLA supplementation increases Na,K-ATPase activity and expression in diabetic rats. In addition, the positive correlation between AA content and Na,K-ATPase activity suggests that in diabetic rats, alterations in membrane fatty acid composition contribute to the decreased Na,K-ATPase activity in outer medulla. J. Nutr. 131: 3160 -3165, 2001.