Table 1. Weights and serum biochemistry for mice on chow or high fat diet for 6 months.
Seven-week-old mice were fed chow (n=8–12) or 45% kcal HFD (n=13–14) for 6 months. Blood was taken 4 weekly with 6 hr fasting blood taken on week 24. p-FDR are false-discovery rate adjusted p-values derived from unpaired T-tests. Values in brackets referred to standard error of the mean. ALT, alanine aminotransferase; AST, aspartate aminotransferase; FGF21, fibroblast growth factor 21; Gdf15, Growth and differentiation factor 15; HOMA-IR, Homeostatic Model Assessment for Insulin Resistance; NEFA, non-esterified fatty acids.
| Chow diet | High-fat diet | |||||
|---|---|---|---|---|---|---|
| WT | Knock-in | p-FDR | WT | Knock-in | p-FDR | |
| Weight (g) | 39.9 (1.2) | 40.9 (1.4) | 1 | 48.4 (1.7) | 45.7 (1.5) | 0.51 |
| Lean mass (g) | 19.97 (0.44) | 20.53 (0.53) | 0.85 | 16.50 (0.39) | 15.51 (0.42) | 0.2 |
| Fat mass (g) | 12.41 (0.97) | 12.67 (1.29) | 1 | 22.39 (1.63) | 24.09 (1.10) | 0.79 |
| Leptin (ug/L) 4 weeks 8 weeks 12 weeks 24 weeks (fasting) |
3.6 (0.9) 4.5 (0.8) 7.6 (0.4) 15.4 (3.4) |
1.3 (0.2) 1.6 (0.3) 2.3 (0.5) 6.0 (1.3) |
0.17 0.056 0.045 0.047 |
14.3 (2.6) 20.8 (3.3) 19.3 (4.0) 57.0 (8.9) |
4.8 (0.5) 8.6 (0.9) 11.4 (1.5) 15.6 (1.5) |
0.01 0.007 0.31 0.003 |
| Adiponectin (mg/L) 4 weeks 8 weeks 12 weeks 24 weeks (fasting) |
24.8 (1.0) 20.0 (0.7) 29.0 (1.4) 29.0 (2.3) |
16.4 (2.3) 11.0 (0.7) 14.7 (0.7) 15.4 (2.3) |
0.068 1.50E-05 4.50E-05 0 |
21.0 (0.4) 29.4 (1.4) 33.0 (0.8) 27.9 (0.9) |
11.0 (3.3) 16.0 (0.7) 18.2 (0.9) 15.5 (0.6) |
4.20E-10 5.30E-07 7.20E-09 4.30E-09 |
| Fgf21 (ng/L) 20 weeks 28 weeks |
238 (26) 444 (51) |
292 (22) 638 (96) |
0.50 0.24 |
2,655 (203) 3,355 (911) |
2,475 (268) 2,919 (289) |
1 1 |
|
Gdf15 (ng/L) (28 weeks) |
132 (6) | 172 (14) | 0.067 | 250 (36) | 217 (23) | 1 |
| Glucose (mmol/L) | 10.0 (0.5) | 10.4 (0.4) | 1 | 11.7 (0.5) | 11.4 (0.5) | 1 |
|
Insulin (µg/L) (33 weeks) |
1.8 (0.3) | 2.0 (0.3) | 1 | 1.7 (0.2) | 1.2 (0.1) | 0.17 |
| HOMA-IR | 141.3 (29.0) | 159.2 (23.3) | 1 | 152.2 (22.9) | 104.8 (12.1) | 0.26 |
|
Insulin (µg/L) (GTT baseline) |
1.8 (0.4) | 2.3 (0.7) | 1 | 2.3 (0.4) | 1.4 (0.1) | 0.1 |
| Lactate (mmol/L) | 4.2 (0.3) | 4.4 (0.2) | 1 | 4.5 (0.4) | 4.8 (0.2) | 1 |
| NEFA (µmol/L) | 1,688 (78) | 1,564 (46) | 0.39 | 922 (87) | 1030 (90) | 0.90 |
| TG (mmol/L) | 1.1 (0.1) | 1.0 (0.1) | 1 | 0.8 (0.1) | 0.7 (0.0) | 0.76 |
| Total cholesterol (mmol/L) | 3.0 (0.1) | 3.1 (0.1) | 1 | 6.3 (0.3) | 5.2 (0.2) | 0.042 |
| ALT (IU/L) | 64 (6) | 68 (5) | 1 | 144 (33) | 45 (9) | 0.076 |
| AST (IU/L) | 114 (20) | 118 (16) | 1 | 207 (32) | 162 (22) | 0.65 |