Exercise training induces alteration of clock genes and myokines expression in tumor-bearing mice

Abstract

To investigate the impact of different exercise training schedules (following a fixed schedule or at random times of the day) on clock genes and myokine expression patterns in the skeletal muscle of tumor-bearing mice. Mice were divided into three groups: tumor (LLC), tumor + exercise training (LLC + T) always performed at the same time of the day (ZT2) and exercise training at random times of the day (ZTAlt). Mice were inoculated subcutaneously with Lewis lung carcinoma cells. The gastrocnemius muscle was dissected and the clock gene expression (Clock/Per1/Per2/Per3/Rev-Erbα/GAPDH) was investigated by quantitative reverse transcription polymerase chain reaction with SYBR® Green. Myokine content in muscle (tumour necrosis factor alpha/IL-10/IL-4) was assessed by enzyme-linked immunosorbent assay. At the end of the protocol, the trained groups showed a reduction in total weight, when compared to Lewis lung carcinoma. Tumor weight was lower in the LLC + T (ZTAlt), when compared to LLC. Clock gene mRNA expression showed a significant increase for ZT20 in the groups that performed physical exercise at LLC + T (ZTAlt), when compared with LLC. The Per family showed increased mRNA expression in ZT4 in both trained mice groups, when compared with LLC. LLC + T (ZTAlt) presented reduction of the expression of anti-inflammatory myokines (Il-10/IL-4) during the night, compared with LLC + T(ZT2). Exercise training is able to induce marked modification of clock gene expression and of the production of myokines, in a way that is dependent on schedule exercise training strategy. Taken together, the results show that exercise is a potent Zeitgeber and may thus contribute to change clock genes expression and myokines that are able to reduce the tumor weight.