Figure 3. Sustained mTORC1 activation in adult mouse hearts induces metabolic remodeling in mTORC1^iSA mice at 12 weeks.

(A) Rates of glucose uptake and (B) glucose oxidation were decreased in retrogradely perfused mTORC1^iSA mouse hearts at 12 weeks (n= 4 Control and 6 mTORC1^iSA mice). (C) G6P metabolite levels were elevated in the heart muscle of mTORC1^iSA mice at 12 weeks (n=5 mice per group). (D) GPI activity is depressed at 12 weeks (n= 5 Control and 6 mTORC1^iSA mice) in mTORC1^iSA and this decrease is sustained through 28 weeks (n= 4 Control and 6 mTORC1^iSA mice). (E) GPI protein levels measured in mTORC1^iSA mouse hearts at 12 weeks (n=6 mice per group) were decreased and this decrease is attenuated at 28 weeks (n= 5 Control and 4 mTORC1^iSA mice). (F) There was no change in the transcription of GPI at either 12 weeks (n= 4 Control and 6 mTORC1^iSA mice) or 28 weeks (n=9 mice per group). (G and H) Levels of ATP, ADP, and AMP, as well as Nicotinamide adenine dinucleotides were similar in mTORC1^iSA than in control mouse hearts at 12 weeks (n=6 mice per group). Nucleotide abundance is expressed as fold-change from control, and was normalized by total peak area and protein concentration. Statistical significance was calculated using two-way ANOVA (A and B), unpaired two-tailed Student’s t test (C), two-way ANOVA with Bonferroni’s multiple comparisons test (D and F), unpaired two-tailed Student’s t test with correction for multiple comparisons using a FDR of 0.1 (G-H); *p<0.05, **p<0.01.