Table 2.
Comparison of MCC950-treateda mice to untreated mice fed a HFHC diet for 6 months
| Genetic Background | C57BL/6J | C57BL/6J | C57BL/6J | C57BL/6J |
|---|---|---|---|---|
| Diet | HFHC 0.75% Cholesterol |
HFHC 0.75% Cholesterol |
HFHC 0.5% Cholesterol |
HFHC 0.5% Cholesterol |
| MCC950 treatment | No | Yes | No | Yes |
| Number of mice | 11 | 10 | 9 | 8 |
| Body weight (g) | 48.7± 4.0 | 45.9 ± 4.2 | 43.5 ± 5.0 | 44.9 ± 7.9 |
| Liver weight (g) | 4.4 ± 0.9 | 3.6 ± 0.9b | 2.8 ± 1.2 | 3.2 ± 1.7 |
| Liver weight/body weight (%) | 9.0 ± 1.0 | 7.8 ± 1.3b | 6.2 ± 2.2 | 6.8 ± 2.6 |
| Food consumption (g/mouse/day) | 3.1 ± 0.3 | 3.1 ± 0.4 | 3.0 ± 0.3 | 3.0 ± 0.4 |
| Fluid consumption (g/mouse/day) | 2.8 ± 0.2 | 2.9 ± 0.3 | 3.0 ± 0.3 | 3.1 ± 0.4 |
| MCC950 dose (mg/Kg/ day) | None | 19.2 ± 1.9 | None | 20.7± 2.9 |
| Plasma levels (fasting) | ||||
| ALT (U/L) | 365.3 ± 57.1 | 335.1 ± 122.7 | 171.3 ± 215.9 | 186.0 ± 203.8 |
| AST (U/L) | 261.7 ± 44.4 | 269.4 ± 156.1 | 139.3 ± 135.3 | 146.2 ± 128.6 |
| ALP (U/L) | 216.9 ± 30.1 | 199.0 ± 53.4 | 126.4 ± 50.1 | 140.5 ± 65.0 |
| Cholesterol (mg/dl) | 323.1 ± 38.5 | 232.5 ± 93.3c | 196.9 ± 58.1 | 205.2 ± 117.8 |
| Triglyceride (mg/dl) | 43.7 ± 9.1 | 38.5 ± 9.5 | 46.0 ± 13.9 | 44.8 ± 19.1 |
| Glucose (mg/dl) | 293.9 ± 33.3 | 248.8 ± 44.7b | 289.2 ± 49.6 | 304.0 ± 28.2 |
| Hepatic histology, n (%) | ||||
| Steatosis grade | ||||
| 0 | 0 (0%) | 0 (0%) | 2 (22%) | 2 (25%) |
| 1 | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| 2 | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| 3 | 11 (100%) | 10 (100%) | 7 (78%) | 6 (75%) |
| Inflammation grade | ||||
| 0 | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| 1 | 0 (0%) | 0 (0%) | 0 (0%) | 2 (25%) |
| 2 | 0 (0%) | 0 (0%) | 4 (44%) | 1 (12%) |
| 3 | 11 (100%) | 10 (100%) | 5 (56%) | 5 (63%) |
| Fibrosis stage | ||||
| 0 | 4 (36%) | 7 (70%) | 2 (22%)/ | 2 (25%) |
| 1 | 7 (64%) | 3 (30%) | 7 (78%) | 5 (63%) |
| 2 | 0 (0%) | 0 (0%) | 0 (0%) | 1 (12%) |
| 3 | 0 (0%) | 0 (0%) | 0 (0%) | 0 (0%) |
| Sirius red staining (fibrosis), % area | 0.37 ± 0.44 | 0.17 ± 0.12 | 0.16 ± 0.14 | 0.31 ± 0.35 |
| Hepatic cholesterol crystals | Very common | Very common | Uncommon/ widely scattered | Uncommon/ widely scattered |
| Hepatic lipids (mg/ g liver) | ||||
| Cholesterol ester | 72.1 ± 13.3 | 52.0 ± 14.7c | 19.1 ± 15.2 | 26.6 ± 31.4 |
| Free cholesterol | 1.17 ± 0.60 | 0.78 ± 0.22 | 0.57 ± 0.49 | 0.45 ± 0.36 |
| Triacylglycerides | 108.2 ± 36.2 | 110.4 ± 24.4 | 122.4 ± 42.3 | 76.1 ± 48.4 |
| Diacylglycerides | 0.35 ± 0.29 | 0.27 ± 0.09 | 0.15 ± 0.07 | 0.21 ± 0.14 |
ALT, alanine aminotransferase; AST, aspartate aminotransferase; ALP, alkaline phosphatase; HFHC, high-fat, high-cholesterol.
a
MCC950 was dissolved in the drinking water of the mice at a concentration of 0.3 mg/ml.
b
t-test P < 0.05 compared to No MCC950 group.
c
t-test P < 0.01 compared to No MCC950 group.