Figure 5. Insulin resistance and mTORC1 hyperactivation in AdicerKO mice. Twelve-week old mice were subjected to ad libitum (AL) or dietary restriction (DR) regimens for one (A,B) or three (C-F) months. (A) Insulin tolerance test (N=5-7 per condition). * P < 0.05 Lox DR vs. AdicerKO DR; † P < 0.05, †† P < 0.01, ††† P < 0.001 Lox AL vs. Lox DR; ‡ P < 0.05, ‡‡ P < 0.01, ‡‡‡ P < 0.001 AdicerKO AL vs. AdicerKO DR. (B-D) Western blots of tissue extracts when (B) insulin was injected in the inferior vena cava and WAT was collected 5 minutes after, or (C,D) at basal, random fed state. WAT, inguinal white adipose tissue. Muscle, gastrocnemius. +, the presence of the protein or intervention. -, the absence of the protein or intervention. pS6, phospho-S6. pAkt, phospho-Akt. pErk1/2, phospho-Erk1/2. Numbers are quantitation of blots (fold expression in comparison to control group) ± SEM. * P < 0.05 for genotype effect; † P < 0.05 for diet effect. (E,F) Mice subjected to AL (E) or DR (F) diets were treated with Rapamycin for 2h prior to an insulin tolerance test (N=3-5 per condition). Mean ± SEM. * P < 0.05, *** P < 0.001 Lox vs. AdicerKO; † P < 0.05, †† P < 0.01 Lox + Rapamycin vs. AdicerKO + Rapamycin.