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. 2022 Jan 26;12:757228. doi: 10.3389/fendo.2021.757228

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Copyright © 2022 Martin, Chuah, Abdelaal, Pedersen, Malmodin, Abrahamsson, Hutter, Godson, Brennan, Fändriks, le Roux and Docherty

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Changes in glomerular volume and their relationship to renal cortical FAO transcripts and urinary nicotinamide and TCA cycle metabolites. (A) Representative images (20x, scale bar 100µm) of haematoxylin and eosin-stained kidney sections from the four experimental groups. (B) Glomerular volume (µm³) was assessed in 30 glomeruli from 6-8 animals per group. Data are plotted as violin plots with individual glomerular measurements superimposed. Within each group, each animal is identified as its own column of dots with a unique colour shade. Median group values are identified by the horizontal black line in each violin and printed on each violin. Statistical significance of between-group differences derived from multiplicity-corrected Wilcoxon rank-sum tests is presented. Statistical significance is denoted as follows: ns = not significant; * = p <0.05; ** = p <0.01; *** = p <0.001; **** = p <0.0001. (C) Correlation plots highlighting Pearson correlation r values for glomerular volume correlations with renal cortical transcripts and urinary metabolites. Regularized log-transformed gene expression counts were used for gene-structure correlations. Transcripts plotted are those which resulted in enrichment of peroxisomal and mitochondrial lipid metabolism pathways in RYGB-FMRR rats (also highlighted in the circular network plot in Figure 2D ). PQN-normalized urinary ¹H-NMR peaks from samples obtained at 4 weeks after intervention were used for metabolite-structure correlations. Metabolites involved in nicotinamide metabolism (PPARα biomarkers) and TCA cycle intermediates, many of which were differentially abundant between RYGB-FMRR and RYGB rats, are plotted. Individual cells in the correlation plots are scaled by colour indicating strength and directionality of the correlation. PPARα, peroxisome proliferator-activated receptor-alpha; RYGB, Roux-en-Y gastric bypass; RYGB-FMRR, Roux-en-Y gastric bypass plus fenofibrate, metformin, ramipril, and rosuvastatin; SD, Sprague Dawley; SHAM, sham surgery (laparotomy); TCA, tricarboxylic acid.