|Appears in Collections:||Faculty of Health Sciences and Sport Journal Articles|
|Peer Review Status:||Refereed|
|Title:||Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise|
Oikawa, Sara Y
Ruegg, Markus A
Hamilton, David Lee
Phillips, Stuart M
|Citation:||Hodson N, McGlory C, Oikawa SY, Jeromson S, Song Z, Ruegg MA, Hamilton DL, Phillips SM & Philp A (2017) Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise, American Journal of Physiology - Cell Physiology, 313 (6), pp. C604-C611.|
|Abstract:||Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 (mTORC1-Raptor positive) regulates skeletal muscle growth, whereas mTORC2 (Rictor positive) regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilised immunohistochemical analysis to study the localisation of mTOR complexes prior to and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in unilateral exercise model. In basal samples, mTOR and the lysosomal marker LAMP2 were highly co-localized and remained so throughout. In the FED and EXFED states, mTOR/LAMP2 complexes were redistributed to the cell periphery (WGA positive staining) (time effect; p=.025), with 39\% (FED) and 26\% (EXFED) increases in mTOR/WGA association observed 1h post-feeding/exercise. mTOR/WGA colocalisation continued to increase in EXFED at 3h (48\% above baseline) whereas colocalisation decreased in FED (21\% above baseline). A significant effect of condition (p=.05) was noted suggesting mTOR/WGA co-localization was greater during EXFED. This pattern was replicated in Raptor/WGA association, where a significant difference between EXFED and FED was noted at 3h post-exercise/feeding (p=.014). Rictor/WGA colocalization remained unaltered throughout the trial. Alterations in mTORC1 cellular location coincided with elevated S6K1 kinase activity, which rose to a greater extent in EXFED compared to FED at 1h post-exercise/feeding (p<.001), and only remained elevated in EXFED at the 3h time point (p=.037). Collectively these data suggest that mTORC1 redistribution within the cell is a fundamental response to resistance exercise and feeding, whereas mTORC2 is predominantly situated at the sarcolemma and does not alter localisation.|
|Rights:||This item has been embargoed for a period. During the embargo please use the Request a Copy feature at the foot of the Repository record to request a copy directly from the author. You can only request a copy if you wish to use this work for your own research or private study. Publisher policy allows this work to be made available in this repository. Published in American Journal of Physiology - Cell Physiology by American Physiological Society. The version of record is available at: http://www.physiology.org/doi/abs/10.1152/ajpcell.00176.2017|
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