Nocturnal fructose feeding increases renal ACE2 activity in mice

Abstract

The objective was to study renal morphology and angiotensin converting enzyme (ACE) activity in an animal model of metabolic syndrome. C57Bl/6 male mice were given: 1) tap water 2) 24 h access to 10% fructose water or 3) 12 h access to fructose water (dark period) and water (light period) for 8 weeks. Regular chow was available ad libitum. Mice on 12 h fructose consumed more total fructose and gained more weight than those with 24 h access. Upon conclusion of the dietary regimen, kidneys were collected for morphologic studies using PAS staining, immunohistochemical staining for ACE and ACE2 and ACE/ACE2 activity. ACE/ACE2 enzyme activity was measured using a mass spectrometric assay with endogenous peptide substrates. Immunohistochemical staining showed a stronger presence of ACE2 in the 12 h group over control and 24 h. ACE staining appeared unchanged. ACE2 activity in the 12 h group was 4 fold higher than in control and 24 h groups (C = 0.6±0.2, 24h = 0.6±0.08 vs. 12h = 2.5±0.4; p<0.05). ACE activity was not different between groups. Pathological changes were unremarkable except for mesangial expansion in the 12 h (C = 0.84±0.01, 24h = 0.88±0.01 vs. 12h = 0.92±0.009; p<0.05). Results document that the renal effects of fructose water are dependent on the timing and volume of consumption. Increased nocturnal fructose water intake is associated with elevated ACE2 activity without changes in ACE. Supported by NIH grant R01 HL09356