Fig. 2. mTORC2 supports mitochondrial respiration and triglyceride disposal during fasting.

a, Generation of liver-specific knockout (KO) of Rictor, Tsc1 or Raptor. b, Representative immunoblots to validate deletion of Rictor gene in livers of 4–6-month-old Rictor^KO male and female mice. Quantifications and percentage reduction of protein levels for RICTOR and P-AKT^Ser473/AKT in Rictor^KO livers are shown (n = 12 mice). c,d, Liver triglyceride (TGs) in 3–7-month-old Con, Tsc1^KO and Raptor^KO (c) or 4–5-month-old Con and Rictor^KO (d) male and female mice that were fed or fasted for 14–16 h. N values for number of mice per group are indicated in parentheses. For c, fed Con (n = 27), fasted Con (n = 11) and fed or fasted Tsc1^KO or Raptor^KO mice (n = 4). For d, fed Con (n = 24), fasted Con (n = 13), fed Rictor^KO (n = 23) and fasted Rictor^KO (n = 12). e, Representative Oil Red O stains in livers of 6-month-old Con or Rictor^KO male mice fasted for 14–16 h (n = 5 mice). f, Serum FFA levels in fed or 14–16 h fasted 3–6-month-old Con or Rictor^KO male mice. Fed Con (n = 8), fasted Con (n = 9), fed Rictor^KO (n = 7) and fasted Rictor^KO (n = 5) mice. g, Area under curve (AUC) for OCRs in Con and Rictor^KO livers from fed or 14–16 h fasted mice. Fed Con (n = 12), fasted Con (n = 11), fed Rictor^KO (n = 12) and fasted Rictor^KO (n = 10) mice. h, Acylcarnitine (AC) content in livers of 4–5-month-old Con or Rictor^KO male mice (n = 4 mice). i, MitoTracker CMXRos fluorescence in serum-deprived and OA-treated siControl (siCon) or siRictor NIH3T3 cells (siCon 59 cells and siRictor 59 cells from n = 3 independent experiments). j, Representative 3D-TEM images of mitochondria in livers of 4–5-month-old Con or Rictor^KO male mice (n = 3 mice). Please refer to Supplementary Video 1 (Con) and Supplementary Video 2 (Rictor^KO). Ponceau is loading control. Individual replicates and means are shown. *P < 0.05, **P < 0.01, ***P < 0.001 and ****P < 0.0001, two-tailed unpaired Student’s t-test (b, h and i); two-way ANOVA followed by Tukey’s multiple comparisons test (c, d and g). Please refer to Supplementary Table 10 statistical summary. Source numerical data are available in Source Data Extended Data Table 1, and unprocessed blots are available in the Source Data for this figure.

Source data