Dec 4, 2013 - Associated with Changes in Myostatin. Expression after a Single Bout of Resistance. Exercise in Healthy Young Men. 1,2. Tim Snijders,3,6 Lex ...
The Journal of Nutrition Nutrient Physiology, Metabolism, and Nutrient-Nutrient Interactions
Acute Dietary Protein Intake Restriction Is Associated with Changes in Myostatin Expression after a Single Bout of Resistance Exercise in Healthy Young Men1,2 Tim Snijders,3,6 Lex B. Verdijk,3,6 Bryon R. McKay,4 Joey S.J. Smeets,3,6 Janneau van Kranenburg,3,6 Bart B.B. Groen,3,6 Gianni Parise,4 Paul Greenhaff,5 and Luc J.C. van Loon3,6* 3 NUTRIM School for Nutrition, Toxicology, and Metabolism, Maastricht University, Maastricht, The Netherlands; 4Department of Kinesiology, McMaster University, Hamilton, Ontario, Canada; and 5School of Biomedical Sciences, University of Nottingham, Queen’s Medical Centre, Nottingham, UK
Abstract Skeletal muscle satellite cells (SCs) play an important role in the myogenic adaptive response to exercise. It remains to be established whether nutrition plays a role in SC activation in response to exercise. In the present study, we assessed whether dietary protein alters the SC response to a single bout of resistance exercise. Twenty healthy young (aged 21 6 2 y) males were randomly assigned to consume a 4-d controlled diet that provided either 1.2 g protein kg body weight21 d21 [normal protein diet (NPD)] or 0.1 g protein kg body weight21 d21 [low protein diet (LPD)]. On the second day of the controlled diet, participants performed a single bout of resistance exercise. Muscle biopsies from the vastus lateralis were collected before and after 12, 24, 48, and 72 h of post-exercise recovery. SC content and activation status were determined using immunohistochemistry. Protein and mRNA expression were determined using Western blotting and reverse transcription polymerase chain reaction. The number of myostatin + SCs decreased significantly at 12, 24, and 48 h (range, 214 to 249%; P < 0.05) after exercise cessation, with no differences between groups. Although the number of myostatin + SCs returned to baseline in the type II fibers on the NPD after 72 h of recovery, the number remained low on the LPD. At the 48 and 72 h time points, myostatin protein expression was elevated (86 6 26% and 88 6 29%, respectively) on the NPD (P < 0.05), whereas it was reduced at 72 h (236 6 12% compared with baseline) in the LPD group (P < 0.05). This study demonstrates that dietary protein intake does not modulate the post-exercise increase in SC content but modifies myostatin expression in skeletal muscle tissue. This trial was registered at clinicaltrials.gov as NCT01220037. J. Nutr. 144: 137–145, 2014.
Introduction Skeletal muscle stem cells, also known as satellite cells (SCs)7, are thought to play an important role in the myogenic adaptive response to exercise. SCs reside in a niche between the basal lamina and the sarcolemma of their associated muscle fiber. 1 Author disclosures: T. Snijders, L. B. Verdijk, B. R. McKay, J. S. J. Smeets, J. van Kranenburg, B. B. B. Groen, G. Parise, P. Greenhaff, and L. J. C. van Loon, no conflicts of interest. 2 Supplemental Figures 1–3 and Supplemental Table 1 are available from the ‘‘Online Supporting Material’’ link in the online posting of the article and from the same link in the online table of contents at http://jn.nutrition.org. 6 Present address: Department of Human Movement Sciences, Faculty of Health, Medicine, and Life Sciences, Maastricht University, Maastricht, The Netherlands. 7 Abbreviations used: BW, body weight; Ct, threshold cycle; DAPI, 4#,6-diamidino-2-fenylindool; En%, energy percent; LPD, low protein diet; MRF, myogenic regulatory factor; MyoD, myogenic differentiation; NPD, normal protein diet; SC, satellite cell; 1RM, one-repetition maximum. * To whom correspondence should be addressed. E-mail: L.vanLoon@ maastrichtuniversity.nl.
Normally, SCs remain in a quiescent state, but, in response to exercise and/or muscle damage, SCs can become activated and subsequently proliferate and differentiate. SCs differentiate to form new myofibers, fuse with existing fibers, or return to a quiescent state, replenishing the resident pool of SCs through selfrenewal (1). The progression of SCs through the myogenic program is mediated by the expression of different myogenic regulatory factors (MRFs) [e.g., myogenic differentiation (MyoD), myogenic factor-5, myogenin, and Mrf4]. The activation, proliferation, and differentiation processes of the SCs represent important regulatory steps that ultimately determine their fate in supporting skeletal muscle fiber adaptation. In addition to the MRFs, myostatin has been identified as a key regulator in the SC response to exercise and/or muscle damage. In animal muscle, reduced myostatin expression has been shown to result in substantial muscle hypertrophy (2,3). More recent work by McKay et al. (4) suggests that, in humans, myostatin is a strong negative regulator of the SC myogenic response to an acute bout
ã 2014 American Society for Nutrition. Manuscript received August 19, 2013. Initial review completed September 25, 2013. Revision accepted November 17, 2013. First published online December 4, 2013; doi:10.3945/jn.113.183996.
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of resistance exercise. Accordingly, because myostatin has been reported to negatively regulate SC activation and self-renewal (5), inhibition of myostatin expression may represent an important myogenic stimulus to allow skeletal muscle hypertrophy in response to prolonged resistance exercise training (6). Prolonged resistance exercise training has been well established as an effective interventional strategy to augment skeletal muscle mass and strength (7–9). A single bout of resistance exercise increases muscle protein synthesis as well as breakdown rates, allowing skeletal muscle to recondition (10–12). Ingestion of dietary protein after a single session of resistance exercise further stimulates muscle protein synthesis rate and reduces muscle protein breakdown, allowing net muscle protein accretion (10,12). In accordance, it has been demonstrated that protein supplementation can augment the increase in skeletal muscle mass in response to prolonged resistance exercise training (13). To turn short-term changes in net muscle protein balance into more long-term muscle fiber hypertrophy, additional myonuclei are prerequisite (14,15). Because myonuclei are postmitotic, skeletal muscle SCs are required to provide new myonuclei during post-exercise recovery. It has been well characterized that protein availability can significantly influence muscle protein synthesis rates after exercise (16–18), which may be translated into long-term benefits (13). It could be speculated that dietary protein can also modulate the SC response during post-exercise recovery in a feedforward manner as to prepare the intrinsic potential of the muscle for long-term adaptation. However, no data exist on the influence of protein intake on the acute SC response after exercise. Therefore, in the present study, we assessed SC content and activation status combined with associated myocellular signaling during 3 d of recovery from a single bout of resistance exercise while ingesting a normal protein [13 energy percent (En%)] diet (NPD) or low protein (
