Figure 6.

Decreased Carboxylesterase 1 (CES1) expression is responsible for the impaired lipid droplet breakdown in proximal tubular epithelial cell–specific O-GlcNAc transferase knockout (PTEC-Ogt^y/-) mice. (A) CES1 is a triglyceride hydrolase that hydrolyzes triglyceride to liberate glycerol and fatty acids (FAs). (B–D) Renal CES1 expression in 20-week-old control Ogt^y/f mice and PTEC-Ogt^y/− mice, demonstrated using (B) immunostaining and (C and D) Western blotting, in the kidneys of fasted PTEC-Ogt^y/− mice was lower than in fasted Ogt^y/f mice, regardless of feeding status (n=5 each). Original magnification, ×400. (E) Renal cholesterol ester (CE) concentration and the ratio of cholesterol ester to total cholesterol concentrations were higher in PTEC-Ogt^y/− mice (n=5 per group). (F) Overexpression of CES1 restored triglyceride degradation in the isolated proximal tubular epithelial cells (PTECs) of 20-week-old PTEC-Ogt^y/− mice. Red, green, and blue colors indicate CES1 protein expression, boron-dipyrromethene (BODIPY)–stained lipid droplets, and 4′,6-diamidino-2-phenylindole (DAPI)–stained nuclei, respectively. Original magnification, ×400. (G and H) Overexpression of CES1 (G) restored ATP production (n=5 per group) and (H) inhibited apoptosis, which is indicated by cleavage of caspase 3 in isolated PTECs from the 20-week-old PTEC-Ogt^y/− mice. (I) Renal CES1 mRNA expression in the PTEC-Ogt^y/− mice was lower, regardless of feeding status (n=5 per group). Horizontal bars in the graphs of D, E, G, and I indicate the median values. P<0.05 was considered statistical significance.