Brittany R Counts1, Justin P Hardee2, Dennis K Fix2, Brandon N VanderVeen2, Ryan N Montalvo2, James A Carson1. 1. Integrative Muscle Biology Laboratory, Division of Rehabilitation Sciences, College of Health Professions, University of Tennessee Health Science Center, Memphis TN. 2. Integrative Muscle Biology Laboratory, Department of Exercise Science, University of South Carolina, Columbia, SC.
Abstract
INTRODUCTION: Cancer cachexia is characterized by severe skeletal muscle mass loss, which is driven by decreased muscle protein synthesis and increased protein degradation. Daily physical activity and feeding behaviors exhibit diurnal fluctuations in mice that can impact the systemic environment and skeletal muscle signaling. PURPOSE: We investigated the effect of cancer cachexia on the diurnal regulation of feeding, physical activity, and skeletal muscle mTORC1 signaling in tumor bearing mice. We also examined the impact of increased physical activity on diurnal behaviors and skeletal muscle mTROC1 signaling in the cancer environment. METHODS: Physical activity and feeding behaviors were measured for 4 consecutive days prior to sacrifice in male C57BL/6 (B6; N=24) and ApcMin/+ (MIN; N=22) mice at 7:00AM and 7:00PM under ad libitum condition. A subset of B6 (N=16) and MIN (N=19) mice were given wheel access for 2-weeks prior to diurnal behavior measurements. Gastrocnemius muscle protein expression was examined. RESULTS: MIN mice demonstrated altered diurnal fluctuations in feeding and activity, compared to the B6. Interestingly, cachexia did not alter MIN total food intake, but dramatically reduced cage physical activity. As a measurement of mTORC1 activity, 4E-BP1 phosphorylation increased following the dark cycle in B6 and pre-cachectic MIN mice, while rpS6 phosphorylation was only increased following the dark cycle in MIN mice. MIN 4E-BP1 phosphorylation at the end of the light cycle was significantly correlated with cachexia progression and reduced physical activity. Voluntary wheel running increased light cycle MIN 4E-BP1 phosphorylation and attenuated muscle mass loss. CONCLUSION: The cancer environment can alter diurnal feeding and physical activity behaviors in tumor bearing mice, which are linked to the progression of cachexia and muscle wasting. Furthermore, suppressed physical activity during cachexia is associated with decreased skeletal muscle mTORC1 signaling.
INTRODUCTION: Cancer cachexia is characterized by severe skeletal muscle mass loss, which is driven by decreased muscle protein synthesis and increased protein degradation. Daily physical activity and feeding behaviors exhibit diurnal fluctuations in mice that can impact the systemic environment and skeletal muscle signaling. PURPOSE: We investigated the effect of cancer cachexia on the diurnal regulation of feeding, physical activity, and skeletal muscle mTORC1 signaling in tumor bearing mice. We also examined the impact of increased physical activity on diurnal behaviors and skeletal muscle mTROC1 signaling in the cancer environment. METHODS: Physical activity and feeding behaviors were measured for 4 consecutive days prior to sacrifice in male C57BL/6 (B6; N=24) and ApcMin/+ (MIN; N=22) mice at 7:00AM and 7:00PM under ad libitum condition. A subset of B6 (N=16) and MIN (N=19) mice were given wheel access for 2-weeks prior to diurnal behavior measurements. Gastrocnemius muscle protein expression was examined. RESULTS: MIN mice demonstrated altered diurnal fluctuations in feeding and activity, compared to the B6. Interestingly, cachexia did not alter MIN total food intake, but dramatically reduced cage physical activity. As a measurement of mTORC1 activity, 4E-BP1 phosphorylation increased following the dark cycle in B6 and pre-cachectic MIN mice, while rpS6 phosphorylation was only increased following the dark cycle in MIN mice. MIN 4E-BP1 phosphorylation at the end of the light cycle was significantly correlated with cachexia progression and reduced physical activity. Voluntary wheel running increased light cycle MIN 4E-BP1 phosphorylation and attenuated muscle mass loss. CONCLUSION: The cancer environment can alter diurnal feeding and physical activity behaviors in tumor bearing mice, which are linked to the progression of cachexia and muscle wasting. Furthermore, suppressed physical activity during cachexia is associated with decreased skeletal muscle mTORC1 signaling.
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