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Fig. 7
Figure 7.Calorie restriction ameliorated the pathological and functional changes caused by high-calorie diets. A: schematic of overfeeding and calorie restriction. Zebrafish were fed a high-calorie diet for 8 wk and then either continued on the high-calorie diet or transitioned to maintenance calories or calorie restriction for 4 wk and compared with fish fed a control diet throughout the 12 wk. B: high-calorie diet induced significant weight gain. Maintenance and calorie restriction diets resulted in slight weight loss, whereas continued high calorie feeding resulted in continued weight gain. C: glomerulomegaly receded with 4 wk of either maintenance or calorie restriction diet, with glomerular size similar to that of control diet-fed fish. High-calorie diet-fed fish continued to exhibit glomerulomegaly. At least 70 glomeruli from 3–4 fish/group were measured on hematoxylin and eosin (H&E)-stained sections. D: proximal tubular enlargement also returned to normal after 4 wk of maintenance or calorie restriction diet. At least 100 proximal tubules from 3−4 fish/group were measured on H&E-stained slides. E: filtration barrier function was restored after 4 wk of either maintenance or calorie restriction diet. High-calorie diet feeding resulted in the presence of 500-kDa dextran in the proximal tubules and glomerulomegaly at 12 wk. Reducing calories to maintenance or calorie-restricted levels eliminated dysfunctional filtration and resulted in normalization of glomerular size. Scale bars = 20 µm. In B, n = 6 fish/group. In C, >60 glomeruli per group were measured per group. In D, >100 tubular cross sections per group were measured. Data are presented as means ± SD. Statistical tests were as follows: Welch ANOVA with Dunnett’s multiple comparisons test. *P < 0.05 and **P < 0.01. CR, calorie-restrict diet; HC, high-calorie diet; MTN, maintenance diet; ND, normal diet.