Training, Leptin Receptors and SOCS3 in Human Muscle

Abstract

Endurance exercise induces suppressor of cytokine signaling 3 (SOCS3) mRNA expression in rodent skeletal muscle and endurance training overimposed on strength training blunts the hypertrophic response to strength training by an unknown mechanism. The aim of this study was to determine the effects of a concurrent strength and endurance training on fat mass, serum leptin concentration, muscle morphology, and muscle vastus lateralis leptin receptors (OB-Rb) and SOCS3 protein expression. 16 healthy young men were assigned to a control (C; n=7), and to a 12-week weightlifting (3 sessions/week)+endurance training program (T; n=9) group. Training enhanced maximal dynamic strength in lower and upper body exercises (18–54%), reduced fat mass by 1.8 kg and serum leptin concentration per kg of fat mass, and elicited muscle hypertrophy of type 2 (+18.5%, P<0.05) but not of type 1 muscle fibres (+4.6%, P=NS). No significant changes were observed in either OB-Rb or SOCS3 protein expression with training. In conclusion, concurrent strength and endurance training reduces fat mass and serum leptin and the ratio leptin/fat mass without significant effects on vastus lateralis OB-Rb protein expression. Training does not increase the basal expression of SOCS3 protein in humans.

strength - obesity - adipokines - endurance

References

• 1 Adams GR, McCue SA. Localized infusion of IGF-I results in skeletal muscle hypertrophy in rats.  J Appl Physiol. 1998;  84 1716-1722
• 2 Bell GJ, Syrotuik D, Martin TP, Burnham R, Quinney HA. Effect of concurrent strength and endurance training on skeletal muscle properties and hormone concentrations in humans.  Eur J Appl Physiol. 2000;  81 418-427
• 3 Benatti FB, Polacow VO, Ribeiro SM, Gualano B, Coelho DF, Rogeri PS, Costa AS, Lancha Junior AH. Swimming training down-regulates plasma leptin levels, but not adipose tissue ob mRNA expression.  Braz J Med Biol Res. 2008;  41 866-871
• 4 Billat V, Dalmay F, Antonini MT, Chassain AP. A method for determining the maximal steady state of blood lactate concentration from two levels of submaximal exercise.  Eur J Appl Physiol. 1994;  69 196-202
• 5 Bjørbæk C, Lavery HJ, Bates SH, Olson RK, Davis SM, Flier JS, Myers Jr MG. SOCS3 mediates feedback inhibition of the leptin receptor via Tyr985.  J Biol Chem. 2000;  275 40649-40657
• 6 Craig CL, Marshall AL, Sjostrom M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity.  Med Sci Sports Exerc. 2003;  35 1381-1395
• 7 Chan JL, Bluher S, Yiannakouris N, Suchard MA, Kratzsch J, Mantzoros CS. Regulation of circulating soluble leptin receptor levels by gender, adiposity, sex steroids, and leptin: observational and interventional studies in humans.  Diabetes. 2002;  51 2105-2112
• 8 Dyck DJ. Adipokines as regulators of muscle metabolism and insulin sensitivity.  Appl Physiol Nutr Metab. 2009;  34 396-402
• 9 Friedman JE, Ferrara CM, Aulak KS, Hatzoglou M, McCune SA, Park S, Sherman WM. Exercise training down-regulates ob gene expression in the genetically obese SHHF/Mcc-fa(cp) rat.  Horm Metab Res. 1997;  29 214-219
• 10 Fuentes T, Ara I, Guadalupe-Grau A, Larsen S, Stallknecht B, Olmedillas H, Santana A, Helge JW, Calbet JA, Guerra B. Leptin receptor 170 KDa (OB-R170) protein expression is reduced in obese human skeletal muscle: a potential mechanism of leptin resistance.  Exp Physiol. 2010;  95 160-171
• 11 Goldspink G. Changes in muscle mass and phenotype and the expression of autocrine and systemic growth factors by muscle in response to stretch and overload.  J Anat. 1999;  194 (Pt 3) 323-334
• 12 Greenhalgh CJ, Alexander WS. Suppressors of cytokine signalling and regulation of growth hormone action.  Growth Horm IGF Res. 2004;  14 200-206
• 13 Guadalupe-Grau A, Fuentes T, Guerra B, Calbet JA. Exercise and bone mass in adults.  Sports Med. 2009;  39 439-468
• 14 Guadalupe-Grau A, Perez-Gomez J, Olmedillas H, Chavarren J, Dorado C, Santana A, Serrano-Sanchez JA, Calbet JA. Strength training combined with plyometric jumps in adults: sex differences in fat-bone axis adaptations.  J Appl Physiol. 2009;  106 1100-1111
• 15 Guerra B, Fuentes T, Delgado-Guerra S, Guadalupe-Grau A, Olmedillas H, Santana A, Ponce-Gonzalez JG, Dorado C, Calbet JA. Gender dimorphism in skeletal muscle leptin receptors, serum leptin and insulin sensitivity.  PLoS One. 2008;  3 e3466
• 16 Guerra B, Santana A, Fuentes T, Delgado-Guerra S, Cabrera-Socorro A, Dorado C, Calbet JA. Leptin receptors in human skeletal muscle.  J Appl Physiol. 2007;  102 1786-1792
• 17 Harriss DJ, Atkinson G. International Journal of Sports Medicine – Ethical Standards in Sport and Exercise Science Research.  Int J Sports Med. 2009;  30 701-702
• 18 Hawley JA. Molecular responses to strength and endurance training: are they incompatible?.  Appl Physiol Nutr Metab. 2009;  34 355-361
• 19 Hickson RC. Interference of strength development by simultaneously training for strength and endurance.  Eur J Appl Physiol. 1980;  45 255-263
• 20 Hilton LK, Loucks AB. Low energy availability, not exercise stress, suppresses the diurnal rhythm of leptin in healthy young women.  Am J Physiol. 2000;  278 E43-E49
• 21 Hukshorn CJ, Westerterp-Plantenga MS, Saris WH. Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men.  Am J Clin Nutr. 2003;  77 771-776
• 22 Kang J, Rashti SL, Tranchina CP, Ratamess NA, Faigenbaum AD, Hoffman JR. Effect of preceding resistance exercise on metabolism during subsequent aerobic session.  Eur J Appl Physiol. 2009;  107 43-50
• 23 Karvonen MJ, Kentala E, Mustala O. The effects of training on heart rate; a longitudinal study.  Ann Med Exp Biol Fenn. 1957;  35 307-315
• 24 Kile BT, Alexander WS. The suppressors of cytokine signalling (SOCS).  Cell Mol Life Sci. 2001;  58 1627-1635
• 25 Kimura M, Tateishi N, Shiota T, Yoshie F, Yamauchi H, Suzuki M, Shibasaki T. Long-term exercise down-regulates leptin receptor mRNA in the arcuate nucleus.  Neuroreport. 2004;  15 713-716
• 26 Kraemer RR, Chu H, Castracane VD. Leptin and exercise.  Exp Biol Med. 2002;  227 701-708
• 27 Kraemer WJ, Ratamess NA. Hormonal responses and adaptations to resistance exercise and training.  Sports Med. 2005;  35 339-361
• 28 Leger B, Derave W, De Bock K, Hespel P, Russell AP. Human sarcopenia reveals an increase in SOCS-3 and myostatin and a reduced efficiency of Akt phosphorylation.  Rejuv Res. 2008;  11 163B-175B
• 29 Leger LA, Lambert J. A maximal multistage 20-m shuttle run test to predict VO₂ max.  Eur J Appl Physiol. 1982;  49 1-12
• 30 Leger LA, Mercier D, Gadoury C, Lambert J. The multistage 20 metre shuttle run test for aerobic fitness.  J Sports Sci. 1988;  6 93-101
• 31 Lieskovska J, Guo D, Derman E. Growth impairment in IL-6-overexpressing transgenic mice is associated with induction of SOCS3 mRNA.  Growth Horm IGF Res. 2003;  13 26-35
• 32 Madiehe AM, Hebert S, Mitchell TD, Harris RB. Strain-dependent stimulation of growth in leptin-treated obese db/db mice.  Endocrinology. 2002;  143 3875-3883
• 33 Nindl BC, Kraemer WJ, Arciero PJ, Samatallee N, Leone CD, Mayo MF, Hafeman DL. Leptin concentrations experience a delayed reduction after resistance exercise in men.  Med Sci Sports Exerc. 2002;  34 608-613
• 34 Olmedillas H, Sanchis-Moysi J, Fuentes T, Guadalupe-Grau A, Ponce-Gonzalez JG, Morales-Alamo D, Santana A, Dorado C, Calbet JA, Guerra B. Muscle hypertrophy and increased expression of leptin receptors in the musculus triceps brachii of the dominant arm in professional tennis players.  Eur J Appl Physiol. 2010;  108 749-758
• 35 Perez-Gomez J, Rodriguez GV, Ara I, Olmedillas H, Chavarren J, Gonzalez-Henriquez JJ, Dorado C, Calbet JA. Role of muscle mass on sprint performance: gender differences?.  Eur J Appl Physiol. 2008;  102 685-694
• 36 Putman CT, Xu X, Gillies E, MacLean IM, Bell GJ. Effects of strength, endurance and combined training on myosin heavy chain content and fibre-type distribution in humans.  Eur J Appl Physiol. 2004;  92 376-384
• 37 Sainz N, Rodriguez A, Catalan V, Becerril S, Ramirez B, Gomez-Ambrosi J, Fruhbeck G. Leptin administration favors muscle mass accretion by decreasing FoxO3a and increasing PGC-1alpha in ob/ob mice.  PLoS One. 2009;  4 e6808
• 38 Sale DG, Jacobs I, MacDougall JD, Garner S. Comparison of two regimens of concurrent strength and endurance training.  Med Sci Sports Exerc. 1990;  22 348-356
• 39 Sale DG, MacDougall JD, Jacobs I, Garner S. Interaction between concurrent strength and endurance training.  J Appl Physiol. 1990;  68 260-270
• 40 Sanchis-Moysi J, Idoate F, Olmedillas H, Guadalupe-Grau A, Alayon S, Carreras A, Dorado C, Calbet JA. The upper extremity of the professional tennis player: muscle volumes, fiber-type distribution and muscle strength.  Scand J Med Sci Sports. 2009;  20 524-534
• 41 Serrano AL, Baeza-Raja B, Perdiguero E, Jardi M, Munoz-Canoves P. Interleukin-6 is an essential regulator of satellite cell-mediated skeletal muscle hypertrophy.  Cell Metab. 2008;  7 33-44
• 42 Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Goeke NM, Olson BJ, Klenk DC. Measurement of protein using bicinchoninic acid.  Anal Biochem. 1985;  150 76-85
• 43 Spangenburg EE, Brown DA, Johnson MS, Moore RL. Exercise increases SOCS-3 expression in rat skeletal muscle: potential relationship to IL-6 expression.  J Physiol. 2006;  572 839-848
• 44 Steinberg GR, Smith AC, Wormald S, Malenfant P, Collier C, Dyck DJ. Endurance training partially reverses dietary-induced leptin resistance in rodent skeletal muscle.  Am J Physiol. 2004;  286 E57-E63
• 45 Tang Y, Zheng S, Chen A. Curcumin eliminates leptin's effects on hepatic stellate cell activation via interrupting leptin signaling.  Endocrinology. 2009;  150 3011-3020
• 46 Tanner RK, Fuller KL, Ross ML. Evaluation of three portable blood lactate analysers: Lactate Pro, Lactate Scout and Lactate Plus.  Eur J Appl Physiol. 2010;  109 551-559
• 47 Trenerry MK, Carey KA, Ward AC, Farnfield MM, Cameron-Smith D. Exercise-induced activation of STAT3 signaling is increased with age.  Rejuv Res. 2008;  11 717-724
• 48 Yasari S, Wang D, Prud’homme D, Jankowski M, Gutkowska J, Lavoie JM. Exercise training decreases plasma leptin levels and the expression of hepatic leptin receptor-a, -b, and, -e in rats.  Mol Cell Biochem. 2009;  324 13-20
• 49 Yasukawa H, Hoshijima M, Gu Y, Nakamura T, Pradervand S, Hanada T, Hanakawa Y, Yoshimura A, Ross Jr J, Chien KR. Suppressor of cytokine signaling-3 is a biomechanical stress-inducible gene that suppresses gp130-mediated cardiac myocyte hypertrophy and survival pathways.  J Clin Invest. 2001;  108 1459-1467
• 50 Zaccaria M, Ermolao A, Roi GS, Englaro P, Tegon G, Varnier M. Leptin reduction after endurance races differing in duration and energy expenditure.  Eur J Appl Physiol. 2002;  87 108-111
• 51 Zhang Y, Scarpace PJ. The role of leptin in leptin resistance and obesity.  Physiol Behav. 2006;  88 249-256

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