Table 1. Deletion of IRE1² in ApoE knockout mice increases plasma lipids and MTP expression.
Apoe−/− and Ire1b−/−/Apoe−/− male mice were kept on chow diet for 12 months or fed western diet for 6 weeks. Plasma samples from overnight fasted mice, unless otherwise indicated, were used to measure total lipids. To determine postprandial lipids, plasma was collected at 22:00 h (3h after lights were turned off). Intestine and liver samples were used to measure apoB and MTP. Feces collected over 48 h were used to measure lipids.
| Apoe−/−(n) | Ire1b−/−/Apoe−/−(n) | Apoe−/−(n) | Ire1b−/−/Apoe−/−(n) | |
|---|---|---|---|---|
|
Chow diet fed |
Western diet fed |
|||
| Body weight (g) | 32.4 ± 3.3 (8) | 34.1 ± 4.7 (8) | 35.5 ± 4.2 (6) | 34.2 ± 2.9 (8) |
| Plasma glucose (mg/dl) | 191.8 ± 36.8 (8) | 195.6 ± 32.3 (8) | 341.9 ± 65.8 (6) | 410.6 ± 125.6(8) |
| Plasma Phospholipids (mg/dl) | 431.8 ± 32.5 (8) | 471.2 ± 45.2 (8) | 559.2 ± 17.2 (6) | 606.9 ± 106.3(8) |
| Plasma free fatty acids (mg/dl) | 1.15 ± 0.1 (8) | 1.26 ± 0.17 (8) | 2.35 ± 0.23 (6) | 3.31 ± 0.79 (8) |
| Plasma triglycerides (mg/dl) | ||||
| Fasting | 113.5 ± 10.9 (8) | 177.5 ± 16.3 (8)*** | 46.5 ± 16.6 (6) | 104.9 ± 27.8 (8)*** |
| Postprandial | 154.4 ± 31.9 (4) | 262.3 ± 37.4 (4)** | ND | ND |
| Plasma cholesterol (mg/dl) | ||||
| Fasting | 596.5 ± 35.2 (8) | 836.7 ± 72.0 (8)*** | 1298.0 ± 71.4 (6) | 1851.8 ± 212.1(8)*** |
| Postprandial | 716.6 ± 120.1 (4) | 1119.8 ± 161.8 (4)** | ND | ND |
| MTP activity (% Transfer/mg/h) | ||||
| Intestinal | 870.2 ± 30.3 (8) | 1221.3 ± 57.6 (8)*** | 983.5 ± 52.4 (6) | 1387.4 ± 77.4(8)*** |
| Hepatic | 577.0 + 55.8 (8) | 609.8 + 60.7 (8) | 456.5 ± 62.3 (6) | 402.1 ± 43.2 (8) |
| MTP mRNA (fold change) | ||||
| Intestinal | 0.995 ± 0.18 (8) | 1.470 ± 0.12 (8)*** | 1.100 ± 0.27 (6) | 1.794 ± 0.26 (8)** |
| Hepatic | 1.023 ± 0.18 (8) | 1.165 ± 0.26 (8) | 0.965 ± 0.23 (6) | 0.737 ± 0.25 (8) |
| ApoB mRNA (fold change) | ||||
| Intestinal | 1.109 ± 0.38 (8) | 1.045 ± 0.30 (8) | ND | ND |
| Hepatic | 1.062 ± 0.22 (8) | 1.199 ± 0.28 (8) | ND | ND |
| Fecal lipids (µmol/mouse/day) | ||||
| Triglycerides | 3.315 ± 0.480 (6) | 2.520 ± 0.442 (6) * | ND | ND |
| Cholesterol | 0.130 ± 0.022 (6) | 0.088 ± 0.017 (6)** | ND | ND |
Values are mean ± SD.
**
p<0.01 and
***
p<0.001 compared to Apoe−/−. ND, not determined.