Table 2.
In vivo effects of insulin receptor (INSR) and insulin-like growth factor-I receptor (IGF-IR) deletion in AT.
| References | Mice Model | Vector | Location of Deletion | Effects |
|---|---|---|---|---|
| [82,106] | FIRKO | aP2/Cre | aP2 expressing cells | Fat mass (↓) |
| Glucose transport (↓) | ||||
| Suppression of lipolysis | ||||
| Lifespan (↑) | ||||
| [107] | GIRKO | GLUT4/Cre | GLUT4 expressing tissues | Diabetes |
| Insulin-resistant AT | ||||
| Heterogeneous WAT | ||||
| [108,109] | AIRKO | Adiponectin/Cre | Adiponectin expressing cells | Lipodystrophy |
| IR | ||||
| IFG | ||||
| Dyslipidemia | ||||
| FLD | ||||
| Lifespan (↓) | ||||
| [110] | AIRKO | Adiponectin/Cre + tamoxifen | Adiponectin expressing cells | WAT (↓) |
| BAT (↓) | ||||
| Metabolic syndrome | ||||
| AT regeneration after 30 days | ||||
| [111] | PerIRKO | Cre-ER + tamoxifen | Liver, WAT, skeletal muscle |
Diabetes |
| Lifespan (↓) | ||||
| [112] | IGF-IRKO | Not available | Immortalized fetal brown adipocytes |
Death (↑) |
| Survival (↓) | ||||
| [113] | F-IR/IGFRKO | UCP1/Cre | BAT | BAT atrophy |
| Impaired thermogenesis | ||||
| Mitochondrial dysfunction | ||||
| Body fat mass (↑) | ||||
| IR (↑) | ||||
| Susceptibility to obesity | ||||
| [30] | F-IR/IGFRKO | aP2/Cre | aP2 expressing cells | WAT (↓) |
| BAT (↓) | ||||
| Impaired thermogenesis | ||||
| Energy expenditure (↑) | ||||
| [108] | F-IR/IGFRKO | Adiponectin/Cre | Adiponectin expressing cells | WAT (↓) BAT (↓) Impaired thermogenesis Severe diabetes Ectopic lipid accumulation in liver, muscle and pancreatic islets |
↓, decrease; ↑, increase; AT, adipose tissue; AIRKO, adipocyte-specific insulin receptor knockout; aP2, fatty acids binding protein; BAT, brown adipose tissue; Cre, recombinase cre; ER, estrogen receptor; FIRKO, fat-specific insulin receptor knockout; F-IR/IGFRKO, insulin receptor/IGF-IR double knockout; FLD, fatty liver disease; GIRKO, GLUT4-specific insulin receptor knockout; GLUT4, glucose transporter 4; IFG, impaired fasting glucose; IGF-IRKO, IGF-IR knockout; IR, insulin resistance; PerIRKO, peripheral insulin receptor knockout; WAT, white adipose tissue; UCP1, uncoupling protein 1.