TABLE 1.
WAY-362450 activity in the liver of LDLR−/− and apoE−/− 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 | 12.7 ± 3.0 | 102.0 ± 6.3 | 50.3 ± 15.2c | 3.8 ± 0.2 | 27.4 ± 1.8 | 5.4 ± 1.2c | 1.00 ± 0.11b | 0.14 ± 0.02 | 1.03 ± 0.09c | 1.00 ± 0.12 | 0.33 ± 0.05 | 1.34 ± 0.08c |
| Male | 7.5 ± 0.8 | 295.0 ± 14.6 | 21.2 ± 4.4c | 3.1 ± 0.3 | 21.1 ± 2.5 | 3.9 ± 0.3c | 0.44 ± 0.11 | 0.08 ± 0.01 | 0.95 ± 0.14c | 0.55 ± 0.12 | 0.10 ± 0.02 | 0.85 ± 0.07c | |
| apoE−/− | Female | 3.6 ± 0.3 | 12.1 ± 2.2 | 3.7 ± 0.4c | 9.7 ± 0.7 | 19.1 ± 1.7 | 12.5 ± 0.3c | 1.00 ± 0.09b | 0.21 ± 0.02 | 2.42 ± 0.27c | 1.00 ± 0.08 | 0.38 ± 0.05 | 1.78 ± 0.21c |
| Male | 1.2 ± 0.2 | 13.1 ± 6.1 | 4.5 ± 1.0c | 5.5 ± 0.6 | 19.2 ± 2.3 | 4.3 ± 0.2c | 0.57 ± 0.08 | 0.19 ± 0.03 | 3.23 ± 0.35c | 1.48 ± 0.23 | 0.23 ± 0.04 | 1.77 ± 0.25c | |
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.