Figure 7.
O-GlcNAcylation to farnesoid X receptor (FXR) is essential for Carboxylesterase 1 (CES1) expression. (A and B) Fold differences in the renal expression of proteins regulated by (A) FXR and (B) peroxisome proliferator-activated receptor-α (PPARα) in the proteomic data. The expression of FXR-regulated proteins was lower in the kidneys of PTEC-Ogty/− mice, and the expression of PPARα-regulated proteins was inconsistent. (C) Immunoprecipitation studies using RL-2 and FXR antibodies in renal cortex samples from 20-week-old wild-type mice. FXR was O-GlcNAcylated. (D) Immunoprecipitation study using an RL-2 antibody to detect O-GlcNAcylated proteins. Hormone-sensitive lipase (HSL), adipose triglyceride lipase (ATGL), perilipin, carboxylesterase 1 (CES1), and PPARα were not O-GlcNAcylated. (E) FXR agonist (GW4064) treatment significantly increased mRNA expression of CES1 in isolated proximal tubular epithelial cells from 20-week-old Ogty/f mice, but it failed to increase it in cells from PTEC-Ogty/− mice (n=5 per group). Horizontal bars in the graphs of E indicate the median values. P<0.05 was considered statistical significance. IB, immunoblot; IP, immunoprecipitation; KO, knockout.