Circulating Tumor Necrosis Factor Alpha May Modulate the Short-Term Detraining Induced Muscle Mass Loss Following Prolonged Resistance Training

Gerard Mc Mahon, Christopher I Morse, Keith Winwood, Adrian Burden, Gladys Onambele

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5 Citations (Scopus)
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Introduction: Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that has been shown to modulate muscle mass, and is responsive to exercise training. The effects of resistance training (RT) followed by a short period of detraining on muscle size, architecture and function in combination with circulating TNFα levels have not been previously investigated in a young, healthy population. Methods: Sixteen participants (8 males and 8 females) were randomly assigned to a training group (TRA; age 20 ± 3 years, mass 76 ± 7 kg), whilst fourteen participants (7 males and 7 females) age 22 ± 2 years, mass 77 ± 6 kg were assigned to a control group (CON). Measures of vastus lateralis (VL) muscle size (normalized physiological cross-sectional area allometrically scaled to body mass; npCSA), architecture (fascicle length; LF, pennation angle Pθ), strength (knee extensor maximal voluntary contraction; KE MVC), specific force, subcutaneous fat (SF) and circulating TNFα were assessed at baseline (BL), post 8 weeks RT (PT), and at two (DT1) and four (DT2) weeks of detraining. Results: Pooled BL TNFα was 0.87 ± 0.28 pg/mL with no differences between groups. BL TNFα tended to be correlated with npCSA (p = 0.055) and KEMVC (p = 0.085) but not specific force (p = 0.671) or SF (p = 0.995). There were significant (p < 0.05) increases in npCSA compared to BL and CON in TRA at PT, DT1, and DT2, despite significant (p < 0.05) decreases in npCSA compared to PT at DT1 and DT2. There were significant (p < 0.05) increases in LF, Pθ and KE MVC at PT but only LF and torque at DT1. There were no significant (p > 0.05) changes in SF, specific force or TNFα at any time points. There was a significant correlation (p = 0.022, r = 0.57) between the relative changes in TNFα and npCSA at DT2 compared to PT. Discussion: Neither RT nor a period of short term detraining altered the quality of muscle (i.e., specific force) despite changes in morphology and function. TNFα does not appear to have any impact on RT-induced gains in muscle size or function, however, TNFα may play a role in inflammatory-status mediated muscle mass loss during subsequent detraining in healthy adults.

Original languageEnglish
Article number527
Pages (from-to)1-11
Number of pages11
JournalFrontiers in Physiology
Issue numberMAY
Publication statusPublished - 3 May 2019

Bibliographical note

Alves, T., Guarnier, F.A., Campoy, F.A., Gois, M.O., Albuquerque, M.C., Seraphim, P.M., et al. (2013). Strength gain through eccentric isotonic training without changes in clinical signs or blood markers. BMC Musculoskeletal Disorders 14(1), 328. doi: 10.1186/1471-2474-14-328.
Balkwill, F. (2006). TNF-α in promotion and progression of cancer. Cancer and Metastasis Reviews 25(3), 409.
Beyer, I., Mets, T., and Bautmans, I. (2012). Chronic low-grade inflammation and age-related sarcopenia. Current Opinion in Clinical Nutrition & Metabolic Care 15(1), 12-22.
Blazevich, A.J., Cannavan, D., Coleman, D.R., and Horne, S. (2007). Influence of concentric and eccentric resistance training on architectural adaptation in human quadriceps muscles. Journal of Applied Physiology 103(5), 1565.
Bostock, E., Pheasey, C., Morse, C.I., Winwood, K.L., and Onambele-Pearson, G. (2013). Effects of essential amino acid supplementation on muscular adaptations to 3 weeks of combined unilateral glenohumeral & radiohumeral joints immobilisation. Journal of Athletic Enhancement.
Bowen, T.S., Schuler, G., and Adams, V. (2015). Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. Journal of cachexia, sarcopenia and muscle 6(3), 197-207.
Brennan, S.F., Cresswell, A.G., Farris, D.J., and Lichtwark, G.A. (2017). In vivo fascicle length measurements via B-mode ultrasound imaging with single vs dual transducer arrangements. Journal of biomechanics 64, 240-244.
Bruunsgaard, H., Bjerregaard, E., Schroll, M., and Pedersen, B.K.J.J.o.t.A.G.S. (2004). Muscle strength after resistance training is inversely correlated with baseline levels of soluble tumor necrosis factor receptors in the oldest old. 52(2), 237-241.
Chen, S.-E., Jin, B., and Li, Y.-P. (2007). TNF-α regulates myogenesis and muscle regeneration by activating p38 MAPK. American Journal of Physiology-Cell Physiology 292(5), C1660-C1671.
Coffey, V.G., and Hawley, J.A. (2007). The molecular bases of training adaptation. Sports Medicine 37(9), 737-763.
Degens, H., and Alway, S.E. (2006). Control of muscle size during disuse, disease, and aging. International Journal of Sports Medicine 27(02), 94-99.
Degens, H., Mattias, S., Peter, H., Ljungqvist, O., and Larsson, L. (1999). Post-operative effects on insulin resistance and specific tension of single human skeletal muscle fibres. Clinical Science 97(4), 449-455.
Del Vecchio, A., Casolo, A., Negro, F., Scorcelletti, M., Bazzucchi, I., Enoka, R., et al. (2019). The increase in muscle force after 4 weeks of strength training is mediated by adaptations in motor unit recruitment and rate coding. The Journal of physiology.
Erskine, R.M., Jones, D.A., Williams, A.G., Stewart, C.E., and Degens, H. (2010). Resistance training increases in vivo quadriceps femoris muscle specific tension in young men. Acta physiologica 199(1), 83-89.
Esformes, J.I., Narici, M.V., and Maganaris, C.N. (2002). Measurement of human muscle volume using ultrasonography. European journal of applied physiology 87(1), 90-92.
Folland, J.P., and Williams, A.G. (2007). The Adaptations to Strength Training: Morphological and Neurological Contributions to Increased Strength. Sports Medicine 37(2), 145-168.
Franchi, M.V., Atherton, P.J., Reeves, N.D., Flück, M., Williams, J., Mitchell, W.K., et al. (2014). Architectural, functional and molecular responses to concentric and eccentric loading in human skeletal muscle. Acta physiologica 210(3), 642-654.
Franchi, M.V., Raiteri, B.J., Longo, S., Sinha, S., Narici, M.V., and Csapo, R. (2018). Muscle Architecture Assessment: Strengths, Shortcomings and New Frontiers of in Vivo Imaging Techniques. Ultrasound in medicine & biology.
Frontera, W.R., Meredith, C.N., O'Reilly, K.P., Knuttgen, H.G., and Evans, W.J. (1988). Strength conditioning in older men: skeletal muscle hypertrophy and improved function. Journal of Applied Physiology 64(3), 1038-1044.
Greiwe, J.S., Cheng, B., Rubin, D.C., Yarasheski, K.E., and Semenkovich, C.F.J.T.F.J. (2001). Resistance exercise decreases skeletal muscle tumor necrosis factor α in frail elderly humans. 15(2), 475-482.
Guttridge, D.C., Mayo, M.W., Madrid, L.V., Wang, C.-Y., and Baldwin Jr, A.S. (2000). NF-κB-induced loss of MyoD messenger RNA: possible role in muscle decay and cachexia. Science 289(5488), 2363-2366.
Häkkinen, K., and Komi, P.V. (1983). Electromyographic changes during strength training and detraining. Medicine and Science in Sports and Exercise 15(6), 455.
Ihalainen, J.K., Schumann, M., Eklund, D., Hämäläinen, M., Moilanen, E., Paulsen, G., et al. (2018). Combined aerobic and resistance training decreases inflammation markers in healthy men. 28(1), 40-47.
Jaric, S., Mirkov, D., and Markovic, G. (2005). Normalizing physical performance tests for body size: aproposal for standardization. The Journal of Strength & Conditioning Research 19(2), 467-474.
Jespersen, J., Nedergaard, A., Andersen, L., Schjerling, P., and Andersen, J. (2011). Myostatin expression during human muscle hypertrophy and subsequent atrophy: increased myostatin with detraining. Scandinavian journal of medicine & science in sports 21(2), 215-223.
Kalyani, R.R., Corriere, M., and Ferrucci, L. (2014). Age-related and disease-related muscle loss: the effect of diabetes, obesity, and other diseases. The lancet Diabetes & endocrinology 2(10), 819-829.
Kubo, K., Ikebukuro, T., Yata, H., Tsunoda, N., and Kanehisa, H. (2010). Time course of changes in muscle and tendon properties during strength training and detraining. The Journal of Strength & Conditioning Research 24(2), 322.
Lang, C.H., Frost, R.A., Nairn, A.C., MacLean, D.A., and Vary, T.C. (2002). TNF-α impairs heart and skeletal muscle protein synthesis by altering translation initiation. American Journal of Physiology-Endocrinology And Metabolism 282(2), E336-E347.
Li, Y.-P., Chen, Y., John, J., Moylan, J., Jin, B., Mann, D.L., et al. (2005). TNF-α acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1/MAFbx in skeletal muscle. The FASEB journal 19(3), 362-370.
Li, Y.-p., Schwartz, R.J., Waddell, I.D., Holloway, B.R., and Reid, M.B. (1998a). Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-κB activation in response to tumor necrosis factor α. The FASEB journal 12(10), 871-880.
Li, Y., Schwartz, R.J., Waddell, I.D., Holloway, B.R., and Reid, M.B. (1998b). Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-κB activation in response to tumor necrosis factor α. The FASEB journal 12(10), 871-880.
Li, Y.P., and Reid, M.B. (2000). NF-κB mediates the protein loss induced by TNF-α in differentiated skeletal muscle myotubes. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279(4), R1165-R1170.
Libardi, C.A., De, G.S., Cavaglieri, C.R., Madruga, V.A., Chacon-Mikahil, M.J.M., sports, s.i., et al. (2012). Effect of resistance, endurance, and concurrent training on TNF-α, IL-6, and CRP. 44(1), 50-56.
Llovera, M., Garcı́a-Martı́nez, C., Agell, N., López-Soriano, F.J., and Argilés, J.M. (1997). TNF can directly induce the expression of ubiquitin-dependent proteolytic system in rat soleus muscles. Biochemical and Biophysical Research Communications 230(2), 238-241.
Louis, E., Raue, U., Yang, Y., Jemiolo, B., and Trappe, S. (2007). Time course of proteolytic, cytokine, and myostatin gene expression after acute exercise in human skeletal muscle. Journal of Applied Physiology 103(5), 1744-1751.
MacDougall, J., Elder, G., Sale, D., Moroz, J., and Sutton, J. (1980). Effects of strength training and immobilization on human muscle fibres. European Journal of Applied Physiology and Occupational Physiology 43(1), 25-34.
MacDougall, J.D., Gibala, M.J., Tarnopolsky, M.A., MacDonald, J.R., Interisano, S.A., and Yarasheski, K.E. (1995). The time course for elevated muscle protein synthesis following heavy resistance exercise. Canadian Journal of Applied Physiology 20(4), 480-486.
Maganaris, C.N., Baltzopoulos, V., Ball, D., and Sargeant, A.J. (2001). In vivo specific tension of human skeletal muscle. Journal of Applied Physiology 90(3), 865-872.
McMahon, G., Morse, C.I., Burden, A., Winwood, K., and Onambélé, G.L. (2014a). Muscular adaptations and insulin‐like growth factor‐1 responses to resistance training are stretch‐mediated. Muscle a d Nerve 49(1), 108-119.
McMahon, G., Morse, C.I., Winwood, K., Burden, A., and Onambélé, G.L. (2018). Gender associated muscle-tendon adaptations to resistance training. PloS one 13(5), e0197852.
McMahon, G.E., Morse, C.I., Burden, A., Winwood, K., and Onambélé‐Pearson, G.L. (2013). The manipulation of strain, when stress is controlled, modulates in vivo tendon mechanical properties but not systemic TGF‐β1 levels. Physiological reports 1(5), e00091.
McMahon, G.E., Morse, C.I., Burden, A., Winwood, K., and Onambélé, G.L. (2014b). Impact of range of motion during ecologically valid resistance training protocols on muscle size, subcutaneous fat, and strength. The Journal of Strength & Conditioning Research 28(1), 245-255.
Milani, R.V., Mehra, M.R., Endres, S., Eigler, A., Cooper, E.S., Lavie Jr, C.J., et al. (1996). The clinical relevance of circulating tumor necrosis factor-α in acute decompensated chronic heart failure without cachexia. 110(4), 992-995.
Moritani, T., and DeVries, H. (1979). Neural factors versus hypertrophy in the time course of muscle strength gain. American Journal of Physical Medicine 58(3), 115.
Morse, C., Degens, H., and Jones, D. (2007). The validity of estimating quadriceps volume from single MRI cross-sections in young men. European journal of applied physiology 100(3), 267-274. doi: 10.1007/s00421-007-0429-4.
Narici, M., Roi, G., and Landoni, L. (1988). Force of knee extensor and flexor muscles and cross-sectional area determined by nuclear magnetic resonance imaging. European Journal of Applied Physiology and Occupational Physiology 57(1), 39-44.
Onambélé-Pearson, G.L., Breen, L., and Stewart, C.E. (2010a). Influence of exercise intensity in older persons with unchanged habitual nutritional intake: skeletal muscle and endocrine adaptations. AGE 32(2), 139-153.
Onambélé-Pearson, G.L., Breen, L., and Stewart, C.E. (2010b). Influences of carbohydrate plus amino acid supplementation on differing exercise intensity adaptations in older persons: skeletal muscle and endocrine responses. AGE 32(2), 125-138.
Oterdoom, L.H., Gansevoort, R.T., Schouten, J.P., de Jong, P.E., Gans, R.O., and Bakker, S.J. (2009). Urinary creatinine excretion, an indirect measure of muscle mass, is an independent predictor of cardiovascular disease and mortality in the general population. Atherosclerosis 207(2), 534-540.
Paoli, A., Pacelli, Q.F., Neri, M., Toniolo, L., Cancellara, P., Canato, M., et al. (2015). Protein supplementation increases postexercise plasma myostatin concentration after 8 weeks of resistance training in young physically active subjects. Journal of medicinal food 18(1), 137-143.
Peake, J., Nosaka, K.K., Muthalib, M., and Suzuki, K. (2006). Systemic inflammatory responses to maximal versus submaximal lengthening contractions of the elbow flexors.
Pearson, S.J., and Onambele, G.N.L. (2005). Acute changes in knee-extensors torque, fiber pennation, and tendon characteristics. Chronobiology International 22(6), 1013-1027.
Pearson, S.J., and Onambele, G.N.L. (2006). Influence of time of day on tendon compliance and estimations of voluntary activation levels. Muscle a d Nerve 33(6), 792-800.
Pratesi, A., Tarantini, F., and Di Bari, M. (2013). Skeletal muscle: an endocrine organ. Clinical cases in mineral and bone metabolism 10(1), 11.
Rall, L.C., Meydani, S.N., Kehayias, J.J., Dawson‐Hughes, B., and Roubenoff, R. (1996a). The effect of progressive resistance training in rheumatoid arthritis. Increased strength without changes in energy balance or body composition. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology 39(3), 415-426.
Rall, L.C., Roubenoff, R., Cannon, J.G., Abad, L.W., Dinarello, C.A., and Meydani, S.N. (1996b). Effects of progressive resistance training on immune response in aging and chronic inflammation. Medicine and science in sports and exercise 28(11), 1356-1365.
Rantanen, T. (2003). Muscle strength, disability and mortality. Scandinavian journal of medicine & science in sports 13(1), 3-8.
Reeves, N., Maganaris, C., and Narici, M. (2004a). Ultrasonographic assessment of human skeletal muscle size. European journal of applied physiology 91(1), 116-118. doi: 10.1007/s00421-003-0961-9.
Reeves, N.D., Narici, M.V., and Maganaris, C.N. (2004b). Effect of resistance training on skeletal muscle-specific force in elderly humans. Journal of Applied Physiology 96(3), 885-892. doi: 10.1152/japplphysiol.00688.2003.
Solomon, A., and Bouloux, P.J.J.o.E. (2006). Modifying muscle mass–the endocrine perspective. 191(2), 349-360.
Tomeleri, C.M., Ribeiro, A.S., Souza, M.F., Schiavoni, D., Schoenfeld, B.J., Venturini, D., et al. (2016). Resistance training improves inflammatory level, lipid and glycemic profiles in obese older women: A randomized controlled trial. 84, 80-87.
Townsend, J.R., Fragala, M.S., Jajtner, A.R., Gonzalez, A.M., Wells, A.J., Mangine, G.T., et al. (2013). β-HYDROXY-β-METHYLBUTYRATE (HMB)-FREE ACID ATTENUATES CIRCULATING TNF-α AND TNFR1 RECEPTOR EXPRESSION POST-RESISTANCE EXERCISE. American Journal of Physiology-Heart and Circulatory Physiology.
Visser, M., Pahor, M., Taaffe, D.R., Goodpaster, B.H., Simonsick, E.M., Newman, A.B., et al. (2002). Relationship of interleukin-6 and tumor necrosis factor-α with muscle mass and muscle strength in elderly men and women: the Health ABC Study. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 57(5), M326-M332.
Wackerhage, H., Schoenfeld, B.J., Hamilton, D.L., Lehti, M., and Hulmi, J.J.J.J.o.A.P. (2018). Stimuli and sensors that initiate skeletal muscle hypertrophy following resistance exercise.
Walton, J., Roberts, N., and Whitehouse, G. (1997). Measurement of the quadriceps femoris muscle using magnetic resonance and ultrasound imaging. British Journal of Sports Medicine 31(1), 59.
Wang, Y., Wang, H., Hegde, V., Dubuisson, O., Gao, Z., Dhurandhar, N.V., et al. (2013). Interplay of pro-and anti-inflammatory cytokines to determine lipid accretion in adipocytes. International Journal of Obesity 37(11), 1490.
Wickiewicz, T.L., Roy, R.R., Powell, P.L., and Edgerton, V.R. (1983). Muscle architecture of the human lower limb. Clinical Orthopaedics and Related Research (179), 275-283.
Yasuda, T., Loenneke, J.P., Ogasawara, R., and Abe, T. (2015). Effects of short‐term detraining following blood flow restricted low‐intensity training on muscle size and strength. Clinical physiology and functional imaging 35(1), 71-75.
Young, A., Stokes, M., Round, J., and Edwards, R. (1983). The effect of high resistance training on the strength and cross sectional area of the human quadriceps. European Journal of Clinical Investigation 13(5), 411-417.


  • Cytokine
  • Inflammation
  • muscle architecture
  • specific force
  • young
  • Young
  • Muscle architecture
  • Specific force


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