Fructose stimulates phosphorylation and trafficking of the Na/K/2Cl cotransporter in rat thick ascending limbs (1109.2)

Abstract

High fructose consumption affects renal salt handling and is linked to salt‐sensitive hypertension in humans and rodents. The thick ascending limb (TAL) reabsorbs 25% of filtered NaCl via NKCC2. However, the effect of fructose on NKCC2 and TAL NaCl absorption is unknown. We hypothesized that acute and chronic fructose treatment stimulate NKCC2 activity and trafficking in TALs. Acute fructose treatment (20 min) enhanced surface NKCC2 expression (Fructose 1mM= 22 ± 5%, 5mM= 49 ± 10%, 10mM= 101 ± 59%; p<0.05), but did not increase NKCC2 phosphorylation at Ser126, Thre96/101, nor total NKCC2 expression. Fructose (5mM) increased NaCl transport‐related TAL oxygen consumption by 11 ± 3% (p<0.05), and this effect was absent when NKCC2 was blocked by furosemide. In contrast, glucose (5 mM) did not affect surface NKCC2 nor TAL oxygen consumption. When Sprague‐Dawley rats were fed 20% fructose for 1 week, surface‐to‐intracellular NKCC2 increased by 61 ± 23% (p<0.05), Thre96,101 phosphorylation increased by 8 ± 3 fold (p<0.05) but total NKCC2 expression was reduced by 40 ± 9% (p<0.05). We concluded that acute fructose treatment increases surface NKCC2 expression and NaCl transport by TALs. One week on a fructose enriched diet increased NKCC2 trafficking and phosphorylation at Thre96/101. Our data suggest that fructose but not glucose may contribute to salt‐sensitive hypertension by stimulating NKCC2 and NaCl absorption.Grant Funding Source: 1P01HL090550