Figure 4.

11β-HSD1 inhibition lowers serum lipids in murine models of metabolic syndrome or atherosclerosis. Compound 544 (closed bars) was administered twice daily by oral gavage to DIO mice (A and B), HF/STZ mice (C and D), or apoE KO mice (E and F). The effects were compared with affected animals that were dosed with vehicle (light hatched bars) and with control animals (open bars). Controls included baseline 16-wk-old animals for apoE KO mice, lean animals for DIO mice, or chow/saline-treated animals for HF/STZ mice. Animals treated with RU38486 served as a positive control for DIO and HF/STZ models (A–D, dark hatched bars). Compound 544 lowers triglycerides (A, DIO; C, HF/STZ; and E, apoE KO), serum cholesterol (B, DIO and F, apoE KO), and free fatty acids (D, HF/STZ). Data shown are the mean of at least two studies. Statistical significance is calculated between the treatment groups and vehicle controls for DIO, the treated groups and the difference between vehicle and chow /saline controls for HF/STZ, or the difference between vehicle and baseline controls for apoE KO (*, P < 0.05; **, P < 0.005). Values represent the mean ± SEM.