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Cancer Attenuates Nutrient Activation of Skeletal Muscle mTORC1 in Female Mice
Author(s) -
Counts Brittany,
Halle Jessica,
Carson James
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.07089
Subject(s) - mtorc1 , skeletal muscle , endocrinology , medicine , insulin , p70 s6 kinase 1 , biology , chemistry , phosphorylation , protein kinase b , biochemistry
Cancer‐induced metabolic disruptions can alter tissue specific energy demands and has the potential to alter muscle responses to feeding. Mechanistic target of rapamycin complex 1 (mTORC1) signaling axis is activated by nutrient stimuli, and cancer cachexia can suppress basal muscle mTORC1 signaling in mice. However, gaps still remain in our understanding of how the cancer environment effects skeletal muscle nutrient regulation of mTORC1 signaling. Purpose We examined the effect of feeding on skeletal muscle mTORC1 signaling in female tumor bearing mice. Methods Female C57BL/6 (B6) and Apc Min/+ (MIN) mice were fasted for 12‐hrs during the light cycle. Following the 12‐hr fast, mice were given access to a food pellet for 1‐hr (B6 FED:N=7, MIN FED:N=8) or fasted for another hour (B6 FAST:N=6, MIN FAST:N=7). Circulating blood glucose, and plasma IL‐6 and insulin were taken prior to sacrifice. Gastrocnemius muscle was homogenized for protein analysis. Statistical significance was set at p£0.05. Results The MIN FED and MIN FAST groups were not different in percent body weight change, polyp number, plasma IL‐6, and hindlimb muscle mass. 1‐hour food intake was not different between B6 FED and MIN FED mice. Both MIN FED and B6 FED increased stomach mass, blood glucose, and circulating insulin levels. Compared to FAST mice, FED mice increased p70S6K and rpS6 phosphorylation, and was positively associated to insulin in both B6 and MIN mice. 4E‐BP1 phosphorylation was increased in the B6 FED compared to B6 FAST, but this response was blunted in the MIN FED. Additionally, circulating insulin concentration was associated to 4E‐BP1 phosphorylation in the B6 FED, but not in the MIN FED. Conclusion The cancer environment can suppress the nutrient‐induced phosphorylation of skeletal muscle 4E‐BP1. Future studies are warranted to determine if the combination of exercise or muscle contraction can improve skeletal muscle mTORC1’s response to nutrients in the female cancer environment Acknowledgements NCI R01‐CA121249