Mechanotransduction and the regulation of mTORC1 signaling in skeletal muscle

Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin, 2015 Linden Drive, Madison, WI 53706, USA.
The international journal of biochemistry & cell biology (Impact Factor: 4.05). 05/2011; 43(9):1267-76. DOI: 10.1016/j.biocel.2011.05.007
Source: PubMed


Mechanical stimuli play a major role in the regulation of skeletal muscle mass, and the maintenance of muscle mass contributes significantly to disease prevention and issues associated with the quality of life. Although the link between mechanical signals and the regulation of muscle mass has been recognized for decades, the mechanisms involved in converting mechanical information into the molecular events that control this process remain poorly defined. Nevertheless, our knowledge of these mechanisms is advancing and recent studies have revealed that signaling through a protein kinase called the mammalian target of rapamycin (mTOR) plays a central role in this event. In this review we will, (1) discuss the evidence which implicates mTOR in the mechanical regulation of skeletal muscle mass, (2) provide an overview of the mechanisms through which signaling by mTOR can be regulated, and (3) summarize our current knowledge of the potential mechanisms involved in the mechanical activation of mTOR signaling.

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    • "Increased mechanical loading of skeletal muscle is one of the most potent stimuli regulating mTOR activity and subsequent protein synthesis. Loading increases insulin-like growth factor I (IGF-I) signaling through phosphoinositide-dependent protein kinase-1 (PI3K) and protein kinase B (Akt) activation, which subsequently leads to phosphorylation of mTOR and increased translation efficiency of myofibrillar proteins (Hornberger, 2011). In addition to IGFs, focal adhesion kinases associated with integrins are also thought to sense load and activate protein synthesis through mTOR and mTORindependent pathways (Calalb et al., 1995;Gordon et al., 2001;Klossner et al., 2009). "

    Preview · Article · Jan 2016 · Journal of Experimental Biology
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    • "passive or active, muscle shortening or lengthening) sensed by a skeletal muscle, information regarding the mechanical stress is converted into a biochemical process (i.e. mechano-transduction) that results in either protein synthesis or protein breakdown (Hornberger, 2011; Martineau & Gardiner, 2001). Although this process is not well understood, mechanical tension (in some cases producing muscle damage) applied to skeletal muscle structures (i.e. "
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    ABSTRACT: Increases in muscle size and strength are influenced by the mechanical and metabolic stresses imposed by resistance training. Mechanical stress is induced by the use of high-intensity training and it is believed it activates a larger percentage of muscle fibers. Conversely, metabolic stress is generated by high training volumes with moderate intensities using short rest intervals. This training paradigm results in greater fatigue and potentially stimulates a greater anabolic hormone response to exercise. Although evidence exists for both strategies, it still remains inconclusive whether one training paradigm is more advantageous than the other regarding muscle hypertrophy development. In untrained adults, the novelty of most resistance training programs may be sufficient to promote hypertrophy and strength gains, whereas greater training intensity may be more beneficial for trained adults. However, the body of well-designed research in this advanced population is limited. Therefore, the purpose of this brief review is to discuss the merits and limitations of the current evidence. © 2015, University of Zagreb - Faculty of Kinesiology. All rights reserved.
    Full-text · Article · Dec 2015
    • "Despite substantial differences in circulating hormone levels between high and low exercise bouts, there was no difference in the increase in muscle fiber size and strength following training. Surprisingly, the mechanisms that underpin mechanical load-induced mTOR activation have remained largely elusive (Goodman 2014;Hornberger 2011). However , important work by Fang and colleagues (2001) proposed a mechanism of cell growth involving PA. "
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    ABSTRACT: Skeletal muscle mass plays a vital role in locomotion, whole-body metabolic health, and is a positive predictor of longevity. It is well established the mammalian target of rapamycin (mTOR) is a central regulator of skeletal muscle protein turnover. The pursuit to find novel nutrient compounds or functional food sources that possess the ability to activate mTOR and promote skeletal muscle protein accretion has been on going. Over the last decade, a key role has been proposed for the phospholipid phosphatidic acid (PA) in mTOR activation. Mechanical load-induced (i.e., resistance exercise) intramuscular PA can directly bind to and activate mTOR. In addition, PA provided exogenously in cell culture heightens mTOR activity, albeit indirectly. Thus, endogenously generated PA and exogenous provision of PA appear to act through distinct mechanisms that converge on mTOR and, potentially, may amplify muscle protein synthesis. In support of this notion, limited evidence from humans suggests that resistance exercise training combined with oral supplemental PA enhances strength gains and muscle hypertrophy. However, the precise mechanisms underpinning the augmented muscle remodelling response with supplemental PA remain elusive. In this review, we will critically examine available evidence from cell cultures and animal and human experimental models to provide an overview of the mechanisms through which endogenous and exogenous PA may act to promote muscle anabolism, and discuss the potential for PA as a therapeutic tool to maintain or restore skeletal muscle mass in the context of ageing and disease.
    No preview · Article · Sep 2015 · Applied Physiology Nutrition and Metabolism
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