Figure 3.

Exercise Induces TFEB Expression and Nuclear Localization in PGC1α^−/− Muscle

(A) TFEB mRNA levels of PGC1α^−/− muscles infected with AAV2.9 control virus (light gray) or AAV2.9-TFEB (dark gray). Data were compared with TFEB mRNA level of WT mice (white). The levels of TFEB were measured in sedentary condition and post-exercise as indicated. Error bars represent mean ± SE for n = 3; ^∗p < 0.05, ^∗∗∗p < 0.001.

(B) TFEB immunohistochemical analysis of PGC1α^−/− muscles from sedentary and exercised mice. GCN muscle cryosections were immunostained by using anti-TFEB antibody. Control means endogenous TFEB in muscles infected with AAV2.9 control virus. TFEB means the transgene TFEB in muscles infected with AAV2.9-TFEB. Arrows indicate exercise-induced TFEB nuclear localization. The scale bars represent 50 μm.

(C) Analysis of genes related to mitochondrial biogenesis in PGC1α^−/− skeletal muscle infected with AAV2.9 control or with AAV2.9-TFEB virus. The mRNA levels were measured before and after acute exercise, as indicated. Data are shown as mean ± SE, n = 3; ^∗p < 0.05, ^∗∗p < 0.01, ^∗∗∗p < 0.001.

(D and E) Muscle fatigue and physical performance are improved by TFEB expression in PGC1α-deficient muscle.

(D) The mice were systemically injected with AAV2.9-TFEB or AAV2.9 control virus. After 3 weeks from the virus injection, mice were subjected to run until exhaustion, as described in the Experimental Procedures. Data are shown as mean ± SE, n = 6; ^∗p < 0.05.

(E) Soleus muscles were transected by intramuscular injection of AAV2.1-TFEB or AAV2.1 control virus, which resulted in 100% transfection efficacy. Index for fatigue means tetanic muscle force generated after 100 s of stimulation divided by the maximal tetanic tension produced during the fatigue protocol. Data are shown as mean ± SE, n = 4; ^∗p < 0.05, ^∗∗∗p < 0.001.