Reduced food consumption increases water intake and modulates renal aquaporin-1 and -2 expression in autoimmune prone mice

Aquaporin-1(AQP1) and AQP2 are members of the aquaporin family of cell membrane water channel transport proteins and have been implicated in the regulation of renal water excretion. We have previously shown that calorie restriction (CR) relative to ad libitum (AL) feeding extends lifespan and delays the onset of autoimmune kidney disease in lupus-prone (NZBxNZW)F1 (B/W) mice. To determine if AQP1 and/or AQP2 expression is influenced by CR, mice were fed an AL or CR (40% less food) diet until 4 (young) or 9 (old) months of age when mice were sacrificed. Kidneys were removed and the expression of AQP1 and AQP2 was determined at the protein and mRNA levels using western blotting and RT-PCR respectively. While age did not significantly increase AQP1 expression in the AL groups, CR did increase both the protein (1.4-fold) and mRNA (2.4-fold) levels. In old mice, AQP1 expression was higher (1.8-fold) in CR compared to the AL group while CR had no effect in young mice. In contrast, AQP2 showed an age related decrease (55%) in the AL groups and an increase in the protein (8.4-fold) and mRNA (1.7-fold) levels in the CR groups. Relative to AL, CR decreased AQP2 expression at the protein (90%) and mRNA (50%) levels in the young mice while an increase at the protein (2.9-fold) and mRNA (1.9-fold) levels was evident in the old mice. Interestingly, a significant increase in water intake per gram body weight was found in both young and old CR fed mice when compared to their AL counterparts which may contribute to the prevention of autoimmune disease with age and differences in longevity. These data show, for the first time, significant age and diet influences in renal AQP1 and AQP2 expression at both protein and mRNA levels in lupus-prone mice.