Differential localization and anabolic responsiveness of mTOR complexes in human skeletal muscle in response to feeding and exercise

作者：Hodson Nathan; McGlory Chris; Oikawa Sara Y; Jeromson Stewart; Song Zhe; Ruegg Markus A; Hamilton D Lee; Phillips Stuart M; Philp Andrew

来源：American Journal of Physiology - Cell Physiology, 2017, 313(6): C604-C611.

DOI：10.1152/ajpcell.00176.2017

<jats:p> Mechanistic target of rapamycin (mTOR) resides as two complexes within skeletal muscle. mTOR complex 1 [mTORC1–regulatory associated protein of mTOR (Raptor) positive] regulates skeletal muscle growth, whereas mTORC2 [rapamycin-insensitive companion of mTOR (Rictor) positive] regulates insulin sensitivity. To examine the regulation of these complexes in human skeletal muscle, we utilized immunohistochemical analysis to study the localization of mTOR complexes before and following protein-carbohydrate feeding (FED) and resistance exercise plus protein-carbohydrate feeding (EXFED) in a unilateral exercise model. In basal samples, mTOR and the lysosomal marker lysosomal associated membrane protein 2 (LAMP2) were highly colocalized and remained so throughout. In the FED and EXFED states, mTOR/LAMP2 complexes were redistributed to the cell periphery [wheat germ agglutinin (WGA)-positive staining] (time effect; P = 0.025), with 39% (FED) and 26% (EXFED) increases in mTOR/WGA association observed 1 h post-feeding/exercise. mTOR/WGA colocalization continued to increase in EXFED at 3 h (48% above baseline) whereas colocalization decreased in FED (21% above baseline). A significant effect of condition ( P = 0.05) was noted suggesting mTOR/WGA colocalization was greater during EXFED. This pattern was replicated in Raptor/WGA association, where a significant difference between EXFED and FED was noted at 3 h post-exercise/feeding ( P = 0.014). 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 with FED at 1 h post-exercise/feeding ( P &lt; 0.001), and only remained elevated in EXFED at the 3 h time point ( P = 0.037). 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 localization. </jats:p>

• 出版日期2017-12