Fig. 7: TEPP46 administration reversed BCAA supplementation-induced renal injury in HF diet-induced obese mice. | Nature Communications

Fig. 7: TEPP46 administration reversed BCAA supplementation-induced renal injury in HF diet-induced obese mice.

From: Branched-chain amino acids contribute to diabetic kidney disease progression via PKM2-mediated podocyte metabolic reprogramming and apoptosis

Fig. 7

a Pyruvate kinase activity in glomeruli isolated from mice. n = 8 mice per group. b The mRNA expression of Synpo, Nephrin, P-cadherin, and Nphs2. n = 5 mice for Nphs2 in HF/Paired group, n = 6 mice for others. c Representative immunoblotting of Nphs2, Synpo, Chac1 and Trib3 (n = 4 for HF/Paired group, n = 5 for HF/BCAA and HF/BCAA + TEPP46 groups). d Left: Representative immunofluorescence images of Nphs2 (green) and Synpo (red). Right: quantification of Nphs2 and Synpo intensities per glomerulus. In each group, 70 glomeruli from 6 mice were evaluated. e Representative immunostaining images of WT1-positive podocytes and quantification of WT1-positive podocytes in renal sections from mice. In each group, 60-89 glomeruli from 6 mice were evaluated. f Representative images of TUNEL staining and quantification of glomerular apoptotic cells in mouse renal sections. A total of 55-97 glomeruli from 6 mice per group were evaluated. g Representative transmission electron microscopy (TEM) images and quantification of the thickness of the glomerular basement membrane (GBM) and foot process width. An average of 120 measurements were performed for each mouse, n = 8 mice per group. h Representative PAS staining of kidney sections (the arrows indicate tubule casts). i Representative PAS staining of the glomeruli of mice and quantification of mesangial matrix expansion was showed. An average of 60 glomeruli per group was assessed. n = 8 per group. j Oil red O staining of kidney sections and TEM analysis of primary proximal tubular cells from kidney sections. Red triangles indicate lipid droplets. k Renal TG levels in kidney tissue. n = 8. l The kidney weight to body weight ratio. n = 8. m The urinary albumin/creatinine ratio. n = 11 mice per group. n–q Wild type C57BL/6 mice, PKM2f/f, and PKM2f/f Cre+ mice were fed the indicated food for 16 weeks, and TEPP46 were treated daily by oral gavage at 30 mg/kg body weight in indicated group. Plasma uric acid, plasma creatinine, urea nitrogen, and urinary albumin levels were measured. n = 8 per group. The data were presented as mean ± SD, and analyzed by one-way ANOVA.

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