Role Of Bmal1 In Aerobic Exercise Improving Mitochondrial Function In Skeletal Muscle Of Ct26 Tumor-bearing Mice

Mitochondrial dysfunction is one of the main features of the cancer, is also related to the prognosis of patients. Circadian clocks control numerous physiological processes, some studies have shown that the core clock gene BMAL1 may act as a key protein to regulate mitochondrial function. OBJECTIVE: To explore the role of BMAL1 in aerobic exercise improving mitochondrial function in skeletal muscle of CT26 tumor-bearing mice. METHODS: (1) Subjects and groups: A total of 40 BALB/c male mice with 6-week-old were selected. All mice were randomly divided into 4 groups: tumor group (M), exercise pretreatment group (EX-Per), postvaccination exercise group (EX-Post) and lifetime exercise group (EX), each group of 10 animals. After 4 weeks, the mice are injected with cancer cells. (2) Exercise Plan: ① The EX and EX-Pre groups were subjected to aerobic exercise for 4 weeks, the treadmill speed was 13 m/min, 0°, 60 min a day, 5 days a week. ② After inoculation with CT26 tumor cells, the EX and EX-Post groups were subjected to aerobic exercise for 3 weeks, the treadmill speed was 12 m/min, 0°, 30-45 min a day, 5 days a week. (3) Index detection: The mice were weighed and anesthetized. The quadriceps femoris muscles were removed. ① The morphology of skeletal muscle mitochondria was observed by transmission electron microscopy; ② Western Blot analysis of BMAL1 and SUCLG2 protein expression. ③ The co-localization of BMAL1 and SUCLG2 was observed by immunofluorescence. RESULT: (1) Transmission electron microscopy results showed: Compared with the M group, the number of mitochondria in EX, EX-Pre and EX-Post group increased, and the structure of double-layer outer membrane was normal. (2) Western Blot results showed: ①BMAL1: Compared with group M, the expression in EX-Pre, EX and EX-Post group was increased by 1.29 times, 1.62 times and 1.06 times (P < 0.05). ② SUCLG2: Compared with group M, the expression in EX-Pre, EX and EX-Post group was increased by 1.12 times, 1.43 times and 0.62 times (P < 0.05). (3) Co-localization results showed: There were obvious co-localization markers in the EX group, and a few co-localization markers in the EX-Pre and EX-Post group. CONCLUSION: Aerobic exercise can improve skeletal muscle mitochondrial function in mice with different tumor models, which may be related to the expression of SUCLG2 mediated by BMAL1.