Calorie restriction restores the glomerular filtration barrier dysfunction in overfed zMIR/VDBP zebrafish. (A) Experiment schema. Zebrafish with DN were divided into calorie restriction [CR, fed with the same amount as normally fed (NF) fish] and continuously overfeeding (DN) groups. The experiment duration was 6 weeks. Proteinuria measurement was performed at the endpoint, and the renal histopathology was analyzed by H&E staining. (B) CR caused a slight decrease in body weight (BW) compared to that in DN fish (n=6-7). (C) CR caused a significant decrease in fasting blood glucose (FBG) levels compared to those in DN fish (n=6-7). (D) CR treatment significantly decreased proteinuria leakage compared to that in zebrafish with DN (n=6-7). (E) Representative images of the glomeruli of the three groups of zebrafish. CR treatment significantly decreased the glomerular hypertrophy observed in zebrafish with DN. Scale bar: 20 μm. (F) Representative images of the proximal tubule area of the three groups of zebrafish. Scale bar: 20 μm. (G,H) CR treatment resulted in a return to normal glomerular area (G) and proximal tubule size (H). Each group had 45 separate glomeruli and proximal tubules analyzed from three fish in each group. Data are presented as mean±s.e.m. *P<0.05; **P<0.01; ***P<0.001; Bonferroni–Dunn multiple comparisons test.
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