TABLE 3.
WAY-362450 activity in the liver of LDLR−/−SHP−/− and apoE−/−SHP−/− mice
| TG (mg/g) |
Cholesterol (mg/g) |
HMG-CoA Synthase mRNA |
PCSK9 mRNA |
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chowa | Western | Western+450 | Chow | Western | Western+450 | Chow | Western | Western+450 | Chow | Western | Western+450 | ||
| LDLR−/− | Female | 5.2 ± 1.8 | 86.6 ± 18.6 | 30.6 ± 3.0c | 4.6 ± 0.5 | 25.6 ± 4.0 | 14.4 ± 1.5c | 0.89 ± 0.07b | 0.42 ± 0.09 | 1.24 ± 0.20c | 0.80 ± 0.10 | 0.98 ± 0.14 | 1.37 ± 0.21c |
| SHP−/− | Male | 4.3 ± 0.2 | 34.6 ± 18.5 | 53.7 ± 1.0 | 3.3 ± 0.2 | 16.3 ± 1.9 | 4.4 ± 1.0c | 0.29 ± 0.10 | 0.05 ± 0.01 | 1.51 ± 0.23c | 0.53 ± 0.05 | 0.31 ± 0.05 | 1.45 ± 0.20c |
| apoE−/− | Female | 3.7 ± 0.8 | 14.7 ± 2.0 | 9.5 ± 1.0c | 5.3 ± 0.5 | 31.3 ± 4.1 | 8.3 ± 0.9c | 1.65 ± 0.50b | 0.46 ± 0.11 | 3.11 ± 0.39c | 1.72 ± 0.15 | 1.60 ± 0.43 | 2.41 ± 0.3 |
| SHP−/− | Male | 1.4 ± 0.4 | 16.5 ± 2.0 | 5.1 ± 1.3c | 3.8 ± 0.1 | 17.7 ± 0.8 | 4.5 ± 0.3c | 1.87 ± 0.12 | 0.31 ± 0.11 | 3.35 ± 0.32c | 1.40 ± 0.21 | 0.61 ± 0.17 | 1.78 ± 0.18c |
a
Mice were fed a standard chow diet, a Western diet, or a Western diet with WAY-362450 as described in Fig. 2. At the conclusion of the study, hepatic total TG and cholesterol levels were determined.
b
Expression levels in female mice fed the chow diet were defined as 1.00 for LDLR−/− and apoE−/−, respectively.
c
P < 0.05 for effect of WAY-362450.