Jean Farup

Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training-accustomed individuals

The influence of adenosine mono phosphate (AMP)‐activated protein kinase (AMPK) vs Akt‐mammalian target of rapamycin C1 (mTORC1) protein signaling mechanisms on converting differentiated exercise into training specific adaptations is not well‐established. To investigate this, human subjects were divided into endurance, strength, and non‐exercise control groups. Data were obtained before and during post‐exercise recovery from single‐bout exercise, conducted with an exercise mode to which the exercise subjects were accustomed through 10 weeks of prior training. Blood and muscle samples were analyzed for plasma substrates and hormones and for muscle markers of AMPK and Akt‐mTORC1 protein signaling. Increases in plasma glucose, insulin, growth hormone (GH), and insulin‐like growth factor (IGF)‐1, and in phosphorylated muscle phospho‐Akt substrate (PAS) of 160 kDa, mTOR, 70 kDa ribosomal protein S6 kinase, eukaryotic initiation factor 4E, and glycogen synthase kinase 3α were observed after strength exercise. Increased phosphorylation of AMPK, histone deacetylase5 (HDAC5), cAMP response element‐binding protein, and acetyl‐CoA carboxylase (ACC) was observed after endurance exercise, but not differently from after strength exercise. No changes in protein phosphorylation were observed in non‐exercise controls. Endurance training produced an increase in maximal oxygen uptake and a decrease in submaximal exercise heart rate, while strength training produced increases in muscle cross‐sectional area and strength. No changes in basal levels of signaling proteins were observed in response to training. The results support that in training‐accustomed individuals, mTORC1 signaling is preferentially activated after hypertrophy‐inducing exercise, while AMPK signaling is less specific for differentiated exercise.

Muscle morphological and strength adaptations to endurance vs. resistance training

Farup, J, Kjølhede, T, Sørensen, H, Dalgas, U, Møller, AB, Vestergaard, PF, Ringgaard, S, Bojsen-Møller, J, and Vissing, K. Muscle morphological and strength adaptations to endurance vs. resistance training. J Strength Cond Res 26(2): 398–407, 2012—Fascicle angle (FA) is suggested to increase as a result of fiber hypertrophy and furthermore to serve as the explanatory link in the discrepancy in the relative adaptations in the anatomical cross-sectional area (CSA) and fiber CSA after resistance training (RT). In contrast to RT, the effects of endurance training on FA are unclear. The purpose of this study was therefore to investigate and compare the longitudinal effects of either progressive endurance training (END, n = 7) or RT (n = 7) in young untrained men on FA, anatomical CSA, and fiber CSA. Muscle morphological measures included the assessment of vastus lateralis FA obtained by ultrasonography and anatomical CSA by magnetic resonance imaging of the thigh and fiber CSA deduced from histochemical analyses of biopsy samples from m. vastus lateralis. Functional performance measures included &OV0312;;O2max and maximal voluntary contraction (MVC). The RT produced increases in FA by 23 ± 8% (p < 0.01), anatomical CSA of the knee extensor muscles by 9 ± 3% (p = 0.001), and fiber CSA by 19 ± 7% (p < 0.05). RT increased knee extensor MVC by 20 ± 5% (p < 0.001). END increased &OV0312;;O2max by 10 ± 2% but did not evoke changes in FA, anatomical CSA, or in fiber CSA. In conclusion, the morphological changes induced by 10 weeks of RT support that FA does indeed serve as the explanatory link in the observed discrepancy between the changes in anatomical and fiber CSA. Contrarily, 10 weeks of endurance training did not induce changes in FA, but the lack of morphological changes from END indirectly support the fact that fiber hypertrophy and FA are interrelated.

Whey protein hydrolysate augments tendon and muscle hypertrophy independent of resistance exercise contraction mode

In a comparative study, we investigated the effects of maximal eccentric or concentric resistance training combined with whey protein or placebo on muscle and tendon hypertrophy. 22 subjects were allocated into either a high‐leucine whey protein hydrolysate + carbohydrate group (WHD) or a carbohydrate group (PLA). Subjects completed 12 weeks maximal knee extensor training with one leg using eccentric contractions and the other using concentric contractions. Before and after training cross‐sectional area (CSA) of m. quadriceps and patellar tendon CSA was quantified with magnetic resonance imaging and a isometric strength test was used to assess maximal voluntary contraction (MVC) and rate of force development (RFD). Quadriceps CSA increased by 7.3 ± 1.0% (P < 0.001) in WHD and 3.4 ± 0.8% (P < 0.01) in PLA, with a greater increase in WHD compared to PLA (P < 0.01). Proximal patellar tendon CSA increased by 14.9 ± 3.1% (P < 0.001) and 8.1 ± 3.2% (P = 0.054) for WHD and PLA, respectively, with a greater increase in WHD compared to PLA (P < 0.05), with no effect of contraction mode. MVC and RFD increased by 15.6 ± 3.5% (P < 0.001) and 12–63% (P < 0.05), respectively, with no group or contraction mode effects. In conclusion, high‐leucine whey protein hydrolysate augments muscle and tendon hypertrophy following 12 weeks of resistance training – irrespective of contraction mode.

Blood flow restricted and traditional resistance training performed to fatigue produce equal muscle hypertrophy

This study investigated the hypertrophic potential of load‐matched blood‐flow restricted resistance training (BFR) vs free‐flow traditional resistance training (low‐load TRT) performed to fatigue. Ten healthy young subjects performed unilateral BFR and contralateral low‐load TRT elbow flexor dumbbell curl with 40% of one repetition maximum until volitional concentric failure 3 days per week for 6 weeks. Prior to and at 3 (post‐3) and 10 (post‐10) days post‐training, magnetic resonance imaging (MRI) was used to estimate elbow flexor muscle volume and muscle water content accumulation through training. Acute changes in muscle thickness following an early vs a late exercise bout were measured with ultrasound to determine muscle swelling during the immediate 0–48 h post‐exercise. Total work was threefold lower for BFR compared with low‐load TRT (P < 0.001). Both BRF and low‐load TRT increased muscle volume by approximately 12% at post‐3 and post‐10 (P < 0.01) with no changes in MRI‐determined water content. Training increased muscle thickness during the immediate 48 h post‐exercise (P < 0.001) and to greater extent with BRF (P < 0.05) in the early training phase. In conclusion, BFR and low‐load TRT, when performed to fatigue, produce equal muscle hypertrophy, which may partly rely on transient exercise‐induced increases in muscle water content.

Influence of exercise contraction mode and protein supplementation on human skeletal muscle satellite cell content and muscle fiber growth

Skeletal muscle satellite cells (SCs) are involved in remodeling and hypertrophy processes of skeletal muscle. However, little knowledge exists on extrinsic factors that influence the content of SCs in skeletal muscle. In a comparative human study, we investigated the muscle fiber type-specific association between emergence of satellite cells (SCs), muscle growth, and remodeling in response to 12 wk unilateral resistance training performed as eccentric (Ecc) or concentric (Conc) resistance training ± whey protein (Whey, 19.5 g protein + 19.5 g glucose) or placebo (Placebo, 39 g glucose) supplementation. Muscle biopsies (vastus lateralis) were analyzed for fiber type-specific SCs, myonuclei, and fiber cross-sectional area (CSA). Following training, SCs increased with Conc in both type I and type II fibers (P < 0.01) and exhibited a group difference from Ecc (P < 0.05), which did not increase. Myonuclei content in type I fibers increased in all groups (P < 0.01), while a specific accretion of myonuclei in type II fibers was observed in the Whey-Conc (P < 0.01) and Placebo-Ecc (P < 0.01) groups. Similarly, whereas type I fiber CSA increased independently of intervention (P < 0.001), type II fiber CSA increased exclusively with Whey-Conc (P < 0.01) and type II fiber hypertrophy correlated with whole muscle hypertrophy exclusively following Conc training (P < 0.01). In conclusion, isolated concentric knee extensor resistance training appears to constitute a stronger driver of SC content than eccentric resistance training while type II fiber hypertrophy was accentuated when combining concentric resistance training with whey protein supplementation.

Interactions between muscle stem cells, mesenchymal-derived cells and immune cells in muscle homeostasis, regeneration and disease

Recent evidence has revealed the importance of reciprocal functional interactions between different types of mononuclear cells in coordinating the repair of injured muscles. In particular, signals released from the inflammatory infiltrate and from mesenchymal interstitial cells (also known as fibro-adipogenic progenitors (FAPs)) appear to instruct muscle stem cells (satellite cells) to break quiescence, proliferate and differentiate. Interestingly, conditions that compromise the functional integrity of this network can bias muscle repair toward pathological outcomes that are typically observed in chronic muscular disorders, that is, fibrotic and fatty muscle degeneration as well as myofiber atrophy. In this review, we will summarize the current knowledge on the regulation of this network in physiological and pathological conditions, and anticipate the potential contribution of its cellular components to relatively unexplored conditions, such as aging and physical exercise.

Effect of resistance exercise contraction mode and protein supplementation on members of the STARS signalling pathway.

•  Myocellular protein signalling constitutes an important regulatory process influencing skeletal muscle cell size and remodelling as an adaptation to exercise and training. •  Findings suggest that the striated muscle activator of Rho signalling (STARS) pathway is involved in exercise‐induced muscle hypertrophy and/or remodelling, but its regulation by different exercise modes is not well understood. •  In a comparative study including single‐bout exercise and training, we investigated the mRNA and protein regulation of STARS and members of its signalling pathway in response to eccentric versus concentric resistance exercise and protein supplementation. •  Our data show that components of the STARS signalling pathway exhibit transient regulation in response to resistance exercise, but not to resistance training, and show contraction mode‐specific regulation at the level of gene and protein expression. •  The results suggest that STARS signalling is important for the initiation of myocellular adaptations to resistance exercise that are dependent on contraction mode, but independent of protein supplement.

Influence of divergent exercise contraction mode and whey protein supplementation on atrogin-1, MuRF1, and FOXO1/3A in human skeletal muscle

Knowledge from human exercise studies on regulators of muscle atrophy is lacking, but it is important to understand the underlying mechanisms influencing skeletal muscle protein turnover and net protein gain. This study examined the regulation of muscle atrophy-related factors, including atrogin-1 and MuRF1, their upstream transcription factors FOXO1 and FOXO3A and the atrogin-1 substrate eIF3-f, in response to unilateral isolated eccentric (ECC) vs. concentric (CONC) exercise and training. Exercise was performed with whey protein hydrolysate (WPH) or isocaloric carbohydrate (CHO) supplementation. Twenty-four subjects were divided into WPH and CHO groups and completed both single-bout exercise and 12 wk of training. Single-bout ECC exercise decreased atrogin-1 and FOXO3A mRNA compared with basal and CONC exercise, while MuRF1 mRNA was upregulated compared with basal. ECC exercise downregulated FOXO1 and phospho-FOXO1 protein compared with basal, and phospho-FOXO3A was downregulated compared with CONC. CONC single-bout exercise mediated a greater increase in MuRF1 mRNA and increased FOXO1 mRNA compared with basal and ECC. CONC exercise downregulated FOXO1, FOXO3A, and eIF3-f protein compared with basal. Following training, an increase in basal phospho-FOXO1 was observed. While WPH supplementation with ECC and CONC training further increased muscle hypertrophy, it did not have an additional effect on mRNA or protein levels of the targets measured. In conclusion, atrogin-1, MuRF1, FOXO1/3A, and eIF3-f mRNA, and protein levels, are differentially regulated by exercise contraction mode but not WPH supplementation combined with hypertrophy-inducing training. This highlights the complexity in understanding the differing roles these factors play in healthy muscle adaptation to exercise.

Postactivation potentiation: upper body force development changes after maximal force intervention.

Farup, J and Sørensen, H. Postactivation potentiation: upper body force development changes after maximal force intervention. J Strength Cond Res 24(7): 1874-1879, 2010-The neuromuscular phenomenon postactivation potentiation can possibly be used to increase the rate of force development (RFD) and maximal power (Pmax). Various intervention protocols have been examined with varying results. Maximal intervention protocols using 1 repetition maximum (1RM) have been examined in earlier studies in the lower body with positive results, but no studies have investigated maximal protocols on the upper body. Using maximal protocols would furthermore eliminate the uncertainties when expressing intensity as either numbers of RM or percentage of 1RM and hence emphasize standardization. Thus, the aim of this study was to examine the force development characteristics in the upper body after a maximal bench-press intervention. Eight strength trained male athletes performed an intervention protocol consisting of 5× 1RM in the bench press. Pre and post the intervention, a test consisting of either an isometric maximal voluntary contraction or a bench throw was completed to measure isometric RFD (iRFD) or Pmax, respectively. Statistical significance was accepted at p ≤ 0.05. After the intervention, a significant decrease in iRFD was observed. No difference was found in Pmax from pre to post. These results conflict with earlier results found in the lower body using the exact same intervention. It could be speculated if different activation levels in the upper body vs. the lower body could explain the conflicting results. In conclusion, to elicit postactivation potentiation in the upper body, an intervention of maximal intensity is not warranted. The practical applications of these results are that coaches and athletes should be careful to implement maximal resistance to elicit a potentiation until further studies have been conducted in this area.

Similar changes in muscle fiber phenotype with differentiated consequences for rate of force development: Endurance versus resistance training

Resistance training has been shown to positively affect the rate of force development (RFD) whereas there is currently no data on the effect of endurance training on RFD. Subjects completed ten weeks of either resistance training (RT, n=7) or endurance cycling (END, n=7). Pre and post measurements included biopsies obtained from m. vastus lateralis to quantify fiber phenotype and fiber area and isokinetic dynamometer tests to quantify maximal torque (Nm) and RFD (Nm/s) at 0-30, 0-50, 0-100 and 0-200ms during maximal isometric contraction for both knee extensors and flexors. Both groups increased the area percentage of type IIa fibers (p<.01) and decreased the area percentage of type IIx fibers (p=.05), whereas only RT increased fiber size (p<.05). RT significantly increased eccentric, concentric and isometric strength for both knee extensors and flexors, whereas END did not. RT increased 200ms RFD (p<.01) in knee flexor RFD and a tendency towards an increase at 100ms (p<.1), whereas tendencies towards decreases were observed for the END group at 30, 50 and 100ms (p<.1), resulting in RT having a higher RFD than END at post (p<.01). In conclusion, resistance training may be very important for maintaining RFD, whereas endurance training may negatively impact RFD.