Figure 8.

Deficient O-GlcNAcylation exacerbates lipotoxicity-related kidney injury in high-fat diet (HFD)-induced obese type 2 diabetic mice. (A) Renal tubulointerstitial lesions, identified by hematoxylin and eosin (HE) staining and immunostaining for fibronectin and F4/80, were not severe in 18-week-old db/db mice and 32-week-old HFD-fed ApoE^+/+ mice, but they were more severe in 32-week-old HFD-fed ApoE^−/− mice. Renal protein O-GlcNAcylation and carboxylesterase 1 (CES1) expressions were high in db/db mice and HFD-fed ApoE^+/+ mice, but they were lower in HFD-fed ApoE^−/− mice. Original magnification, ×400. (B) HFD intervention study in Ogt^y/f mice and PTEC-Ogt^y/− mice (n=5 per group). (C) Change in mean body mass. PTEC-Ogt^y/− mice showed lower body mass gain during the HFD-feeding period. (D) Change in mean blood glucose concentration during an intraperitoneal insulin tolerance test. There was no significant difference in insulin sensitivity between 24-week-old Ogt^y/f and PTEC-Ogt^y/− mice. (E) Renal tubular cell damage in HE-stained sections was significantly worse in PTEC-Ogt^y/− mice. Original magnification, ×400. (F) Oil-red O staining of positive neutral lipid and fibronectin deposition was higher in the kidneys of PTEC-Ogt^y/− mice, and it was accompanied by lower CES1 expression. Original magnification, ×400. Horizontal bars in E indicate the median values for each group. P<0.05 was considered statistical significance. ND, normal diet; TM, tamoxifen.