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Fig. 6
Figure 6.High-calorie diets led to glomerular filtration barrier dysfunction and susceptibility to injury. A: high-calorie diet feeding resulted in filtration barrier dysfunction. In normal diet-fed fish, no signal was present from 500-kDa dextran uptake in proximal tubules, whereas 70-kDa dextran was filtered and reabsorbed. In high-calorie and high-calorie, high-fat diet-fed fish, the signal from the larger dextran colocalized with the smaller, indicating failure of size exclusion at the glomerulus. Colocalization was demonstrated by Spearman’s ranked correlation coefficient, with 1 = absolute colocalization and 0 = no colocalization. Scatterplots demonstrate the relative intensities of red (x-axis) versus green (y-axis) pixels. B: schematic representation of dietary preconditioning to metronidazole (MTZ) injury. Zebrafish were fed one of four diets for 8 wk prior to treatment with 2 mM MTZ for 24 h and were then allowed to recover for 72 h before euthanasia. C: proximal tubule green fluorescent protein (GFP) fluorescence (arrows) was present after low-dose MTZ injury in fish preconditioned with a high-calorie diet (high-calorie or high-calorie, high-fat diets) but not in those fed a normal diet (arrowheads indicate normal tubules). The high-fat diet-fed group is not shown, as effects were equivalent to normal diet. No fish in the normal diet- or high-fat diet-fed groups had observable GFP in the proximal tubules, while 20% and 40% of those in the high-calorie and high-calorie, high-fat diet-fed groups did, respectively. In C, 5 fish/group were evaluated. Data are presented as percentages of fish with GFP in the proximal tubules. Scale bars = 20 µm. HC, high-calorie diet; HCHF, high-calorie, high-fat diet; HF, high-fat diet; ND, normal diet.