Protein synthesis rates in human muscles: neither anatomical location nor fibre‐type composition are major determinants

Mittendorfer, Bettina; Andersen, Jesper L.; Plomgaard, Peter; Saltin, Bengt; Babraj, John; Smith, Kenneth; Rennie, Michael J.

doi:10.1113/jphysiol.2004.077180

Cited by 101 publications

(114 citation statements)

References 43 publications

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“…This finding is consistent with previous direct measures of FSR in different muscle groups where triceps FSR differed from quadriceps FSR by approximately 15% in healthy individuals (47). The magnitude of the difference in FSR between quadriceps and rectus is, however, small and the clinical significance of the finding is uncertain.…”

Section: Discussionsupporting

confidence: 82%

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

MacDonald

Johns

Stephens

et al. 2015

Clinical Cancer Research

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Purpose: Skeletal muscle wasting and weight loss are characteristic features of cancer cachexia and contribute to impaired function, increased morbidity, and poor tolerance of chemotherapy. This study used a novel technique to measure habitual myofibrillar protein synthesis in patients with cancer compared with healthy controls.Experimental design: An oral heavy water (87.5 g deuterium oxide) tracer was administered as a single dose. Serum samples were taken over the subsequent week followed by a quadriceps muscle biopsy. Deuterium enrichment was measured in body water, serum alanine, and alanine in the myofibrillar component of muscle using gas chromatography-pyrolysisisotope ratio mass spectrometry and the protein synthesis rate calculated from the rate of tracer incorporation. Net change in muscle mass over the preceding 3 months was calculated from serial CT scans and allowed estimation of protein breakdown.Results: Seven healthy volunteers, 6 weight-stable, and 7 weight-losing (!5% weight loss) patients undergoing surgery for upper gastrointestinal cancer were recruited. Serial CT scans were available in 10 patients, who lost skeletal muscle mass preoperatively at a rate of 5.6%/100 days. Myofibrillar protein fractional synthetic rate was 0.058%, 0.061%, and 0.073%/hour in controls, weight-stable, and weight-losing patients, respectively. Weightlosing patients had higher synthetic rates than controls (P ¼ 0.03).Conclusion: Contrary to previous studies, there was no evidence of suppression of myofibrillar protein synthesis in patients with cancer cachexia. Our finding implies a small increase in muscle breakdown may account for muscle wasting.

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Section: Discussionsupporting

confidence: 82%

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

MacDonald

Johns

Stephens

et al. 2015

Clinical Cancer Research

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“…In support of this, several studies have shown that, in animals, muscle composed of mainly type I fibers present much higher basal protein turnover than muscles expressing mainly type II fibers (15,20). However, this conclusion should be taken with caution, since it has been shown in humans that protein synthesis rates at rest in triceps brachii vs. soleus and vastus lateralis, three muscles known to markedly differ in fiber-type composition, were only slightly (i.e., within 15%) different (25).…”

Section: Discussionmentioning

confidence: 77%

Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type

Rose¹,

Bisiani²,

Vistisen³

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Rose AJ, Bisiani B, Vistisen B, Kiens B, Richter EA. Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type. Am J Physiol Regul Integr Comp Physiol 296: R326 -R333, 2009. First published November 26, 2008 doi:10.1152/ajpregu.90806.2008.-Protein synthesis in skeletal muscle is known to decrease during exercise, and it has been suggested that this may depend on the magnitude of the relative metabolic stress within the contracting muscle. To examine the mechanisms behind this, the effect of exercise intensity on skeletal muscle eukaryotic elongation factor 2 (eEF2) and eukaryotic initiation factor 4E binding protein 1 (4EBP1) phosphorylation, key components in the mRNA translation machinery, were examined together with AMP-activated protein kinase (AMPK) in healthy young men. Skeletal muscle eEF2 phosphorylation at Thr 56 increased during exercise but was not influenced by exercise intensity, and was lower than rest 30 min after exercise. On the other hand, 4EBP1 phosphorylation at Thr 37/46 decreased during exercise, and this decrease was greater at higher exercise intensities and was similar to rest 30 min after exercise. AMPK activity, as indexed by AMPK ␣-subunit phosphorylation at Thr 172 and phosphorylation of the AMPK substrate ACC␤ at Ser 221 , was higher with higher exercise intensities, and these indices were higher than rest after high-intensity exercise only. Using immunohistochemistry, it was shown that the increase in skeletal muscle eEF2 Thr 56 phosphorylation was restricted to type I myofibers. Taken together, these data suggest that the depression of skeletal muscle protein synthesis with endurance-type exercise may be regulated at both initiation (i.e., 4EBP1) and elongation (i.e., eEF2) steps, with eEF2 phosphorylation contributing at all exercise intensities but 4EBP1 dephosphorylation contributing to a greater extent at high vs. low exercise intensities. protein synthesis; translation; elongation; initiation; AMPK IT IS RECOGNIZED THAT THE understanding of the mechanisms controlling skeletal muscle protein turnover may aid in the development of novel therapies to combat skeletal muscle diseases (30). The control of protein turnover in skeletal muscle during exercise is poorly understood (30). It is known that skeletal muscle protein synthesis is blunted during exercise (2, 13). A recent study (24) demonstrated that contractile activity was a potent stimulus to blunt net protein synthesis rate of rat skeletal muscle ex vivo and can even override the anabolic effect of insulin. Studies by BylundFellenius et al. (7) in perfused rat hindquarters demonstrated that protein synthesis rates were lower in contracting compared with resting skeletal muscle, particularly in fast-twitch muscles. In that study (7), it was shown that the magnitude of the blunting of protein synthesis was related to the magnitude of changes in high-energy phosphogens, indicating that signaling downstream of metabolic stress is a likely mechanism behind the fall...

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“…In exercise responses, it is generally known that soleus muscle is involved in aerobic exercise, and EDL muscle is involved in resistance exercise (Trappe et al, 2004;Mittendorfer et al, 2005). However, some studies regarding the adaptation of insulin related proteins in the fiber type specific muscles to exercise training is confusing.…”

Section: Discussionmentioning

confidence: 99%

Exercise type and muscle fiber specific induction of caveolin-1 expression for insulin sensitivity of skeletal muscle

Kim²,

Ryu³

et al. 2007

Exp Mol Med

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It is well known that exercise can have beneficial effects on insulin resistance by activation of glucose transporter. Following up our previous report that caveolin-1 plays an important role in glucose uptake in L6 skeletal muscle cells, we examined whether exercise alters the expression of caveolin-1, and whether exercise-caused changes are muscle fiber and exercise type specific. Fifity week-old Sprague Dawley (SD) rats were trained to climb a ladder and treadmill for 8 weeks and their soleus muscles (SOL) and extensor digitorum longus muscles (EDL) were removed after the last bout of exercise and compared with those from non-exercised animals. We found that the expression of insulin related proteins and caveolins did not change in SOL muscles after exercise. However, in EDL muscles, the expression of insulin receptor β (IRβ) and glucose transporter-4 (GLUT-4) as well as phosphorylation of AKT and AMPK increased with resistance exercise but not with aerobic exercise. Also, caveolin-1 and caveolin-3 increased along with insulin related proteins only in EDL muscles by resistance exercise. These results suggest that upregulation of caveolin-1 in the skeletal muscle is fiber specific and exercise type specific, implicating the requirement of the specific mode of exercise to improve insulin sensitivity.

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Protein synthesis rates in human muscles: neither anatomical location nor fibre‐type composition are major determinants

Cited by 101 publications

References 43 publications

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

Habitual Myofibrillar Protein Synthesis Is Normal in Patients with Upper GI Cancer Cachexia

Skeletal muscle eEF2 and 4EBP1 phosphorylation during endurance exercise is dependent on intensity and muscle fiber type

Exercise type and muscle fiber specific induction of caveolin-1 expression for insulin sensitivity of skeletal muscle

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