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Altered thick ascending limb function in aging female mice consuming high quantities of fructose‐sweetened water
Author(s) -
Li Lijun,
Yunghans Allison,
Awan SheharBano,
Alamri Lamia,
Ecelbarger Carolyn
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.1115.13
Subject(s) - endocrinology , urine osmolality , medicine , urine , fructose , kidney , sodium , renal function , cotransporter , chemistry , biochemistry , organic chemistry
Fructose (Frc) is metabolized differently from glucose, i.e., with initial metabolism by ketohexokinase (KHK), an enzyme associated with ATP depletion. To test whether a diet enriched in Frc might impair energy‐intensive actions of the renal thick ascending limb (TAL), we evaluated TAL function and protein expression in response to 4‐weeks of 10% Frc in drinking water in young (Y, 3 months) male (M) and female (F) and mid‐aged F (A, 12 months) mice. Frc resulted in, on average, 11% lower kidney weights, regardless of age or sex. In addition, Frc caused a significant reduction in urine concentrating capacity, observed most dramatically in the aged females (F). Urine osmolality was (% of control): 95, 75, and 44 in YMFrc, YFFrc, and AFFrc, respectively. In contrast, Frc increased urine diluting capacity. However, this protective adaptation was attenuated in the AFFrc (urine osmolality % of C): 77 (YMFrc), 76 (YFFrc), 87 (AFFrc). Western blotting revealed 2–5X increased kidney cortex KHK expression in Frc groups, with the increase greatest in YFFrc. Frc resulted in a modest 20–60% increase in band density for the Na‐K‐2Cl cotransporter (NKCC2), the major apical sodium chloride cotransporter of the TAL, but only in Y mice. In the AFFrc it was reduced 30%. In summary, diets enriched in Frc may alter the ability of the TAL to effectively dilute and concentrate urine. Aging subjects may be especially vulnerable. NIH DK082507.