Post-exercise carbohydrate and energy availability induce independent effects on skeletal muscle cell signalling and bone turnover: implications for training adaptation

Kelly M Hammond, Craig Sale, William Fraser, Jonathan Tang, Sam O Shepherd, Juliette A Strauss, Graeme L Close, Matt Cocks, Julien Louis, Jamie Pugh, Claire Stewart, Adam P Sharples, James P Morton, Kelly M Hammond, Craig Sale, William Fraser, Jonathan Tang, Sam O Shepherd, Juliette A Strauss, Graeme L Close, Matt Cocks, Julien Louis, Jamie Pugh, Claire Stewart, Adam P Sharples, James P Morton

Abstract

Key points: Reduced carbohydrate (CHO) availability before and after exercise may augment endurance training-induced adaptations of human skeletal muscle, as mediated via modulation of cell signalling pathways. However, it is not known whether such responses are mediated by CHO restriction, energy restriction or a combination of both. In recovery from a twice per day training protocol where muscle glycogen concentration is maintained within 200-350 mmol kg-1 dry weight (dw), we demonstrate that acute post-exercise CHO and energy restriction (i.e. < 24 h) does not potentiate potent cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after an acute training session attenuated markers of bone resorption, effects that are independent of energy availability. Whilst the enhanced muscle adaptations associated with CHO restriction may be regulated by absolute muscle glycogen concentration, the acute within-day fluctuations in CHO availability inherent to twice per day training may have chronic implications for bone turnover.

Abstract: We examined the effects of post-exercise carbohydrate (CHO) and energy availability (EA) on potent skeletal muscle cell signalling pathways (regulating mitochondrial biogenesis and lipid metabolism) and indicators of bone metabolism. In a repeated measures design, nine males completed a morning (AM) and afternoon (PM) high-intensity interval (HIT) (8 × 5 min at 85% V̇O2peak ) running protocol (interspersed by 3.5 h) under dietary conditions of (1) high CHO availability (HCHO: CHO ∼12 g kg-1 , EA∼ 60 kcal kg-1 fat free mass (FFM)), (2) reduced CHO but high fat availability (LCHF: CHO ∼3 (-1 , EA∼ 60 kcal kg-1 FFM) or (3), reduced CHO and reduced energy availability (LCAL: CHO ∼3 g kg-1 , EA∼ 20 kcal kg-1 FFM). Muscle glycogen was reduced to ∼200 mmol kg-1 dw in all trials immediately post PM HIT (P < 0.01) and remained lower at 17 h (171, 194 and 316 mmol kg-1 dw) post PM HIT in LCHF and LCAL (P < 0.001) compared to HCHO. Exercise induced comparable p38MAPK phosphorylation (P < 0.05) immediately post PM HIT and similar mRNA expression (all P < 0.05) of PGC-1α, p53 and CPT1 mRNA in HCHO, LCHF and LCAL. Post-exercise circulating βCTX was lower in HCHO (P < 0.05) compared to LCHF and LCAL whereas exercise-induced increases in IL-6 were larger in LCAL (P < 0.05) compared to LCHF and HCHO. In conditions where glycogen concentration is maintained within 200-350 mmol kg-1 dw, we conclude post-exercise CHO and energy restriction (i.e. < 24 h) does not potentiate cell signalling pathways that regulate hallmark adaptations associated with endurance training. In contrast, consuming CHO before, during and after HIT running attenuates bone resorption, effects that are independent of energy availability and circulating IL-6.

Keywords: IL-6; PGC-1α; caloric restriction; βCTX.

© 2019 The Authors. The Journal of Physiology © 2019 The Physiological Society.

References

    1. Ahlborg G, Felig P, Hagenfeldt L, Hendler R & Wahren J (1974). Substrate turnover during prolonged exercise in man. Splanchnic and leg metabolism of glucose, free fatty acids, and amino acids. J Clin Invest 53,1080-1090.
    1. Bartlett JD, Hawley JA & Morton JP (2015). Carbohydrate availability and exercise training adaptation: too much of a good thing? Eur J Sports Sci 15, 3-12.
    1. Bartlett JD, Louhelainen J, Iqbal Z, Cochran AJ, Gibala MJ, Gregson W & Morton JP (2013). Reduced carbohydrate availability enhances exercise-induced p53 signalling in human skeletal muscle: implications for mitochondrial biogenesis. Am J Physiol Regul Integr Comp Physiol 304, R450-R458.
    1. Badenhorst CE, Dawson B, Cox GR, Sim M, Laarakkers CM, Swinkels dw & Peeling P (2016). Seven days of high carbohydrate ingestion does not attenuate post-exercise IL-6 and hepcidin levels. Eur J Appl Physiol 116, 1715-1724.
    1. Bergmann NC, Lund A, Gasbjerg LS, Jørgensen NR, Jessen L, Hartmann B, Holst JJ, Christensen MB, Vilsbøll T & Knop FK (2019). Separate and combined effects of GIP and GLP-1 infusions on bone metabolism in overweight men without diabetes. J Clin Endocrinol Metab 104, 2953-2960.
    1. Bjarnason NH, Henriksen EE, Alexandersen P, Christgau S, Henriksen DB & Christiansen C (2002). Mechanism of circadian variation in bone resorption. Bone, 30, 307-313.
    1. Borg GA (1973). Perceived exertion: a note on ‘history’ and methods. Med Sci Sports 5, 90-93.
    1. Burke LM, Hawley JA, Jeukendrup A, Morton JP, Stellingwerff T & Maughan RJ (2018). Toward a common understanding of diet-exercise strategies to manipulate fuel availability for training and competition preparation in endurance sports. Int J Sports Nutr Exerc Metab 28, 451-463.
    1. Chan MHS, McGee SL, Watt MJ, Hargreaves M & Febbraio MA (2004). Altering dietary nutrient intake that reduces glycogen content leads to phosphorylation of p38MAP kinase in human skeletal muscle: Association with IL-6 gene transcription during contraction. FASEB J 18, 1785-1787.
    1. Chen X, Iqbal N, Boden G (1999). The effects of free fatty acids on gluconeogenesis and glycogenolysis in normal subjects. J Clin Invest 10, 365-372.
    1. Clowes J, Hannon R, Yap T, Hoyle N, Blumsohn A & Eastell R (2002). Effect of feeding on bone turnover markers and its impact on biological variability of measurements. Bone 30, 886-890.
    1. Cochran AJR, Little JP, Tarnopolsky MA & Gibala MJ (2010). Carbohydrate feeding during recovery alters the skeletal muscle metabolic response to repeated sessions of high intensity interval exercise in humans. J Appl Physiol 108, 628-636.
    1. Considine RV, Sinha MK & Heiman ML (1996). Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334, 292-295.
    1. de Sousa MV, Pereira RM, Fukui R, Caparbo VF & da Silva ME (2014). Carbohydrate beverages attenuate bone resorption markers in elite runners. Metab 63, 1536-1541.
    1. DiLorenzo FM, Drager CJ & Rankin JW (2014). Docosahexaenoic acid affects markers of inflammation and muscle damage after eccentric exercise. J Strength Cond Res 28, 2768-2774.
    1. Febbraio MA, Steensberg A, Keller C, Starkie RL, Nielsen HB, Krustrup P, Ott P, Secher NH & Pedersen BK (2003). Glucose ingestion attenuates interleukin-6 release from contracting skeletal muscle in humans. J Physiol 549, 607-612.
    1. Fredericson M, Chew K, Ngo J, Cleek T, Kiratli J & Cobb K (2007). Regional bone mineral density in male athletes: a comparison of soccer players, runners and controls. Br J Sports Med 41, 664-668.
    1. Fudge BW, Westerterp, KR, Kiplamai FK, Onywera VO, Boit MK, Kayser B & Pitsiladis YP (2006). Evidence of negative energy balance using doubly labelled water in elite Kenyan endurance runners prior to competition. Br J Nutr 95, 59-66.
    1. Fujimura R, Ashizawa N, Watanabe M, Mukai N, Hitoshi A, Fukubayashi T, Hayashi K, Tokuyama K & Suzuki M (1997). Effect of resistance exercise training on bone formation and resorption in young male subjects assessed by biomarkers of bone metanolism. J Bone Min Res 12, 656-662.
    1. Gejl KD, Tharns LB, Hansen M, Rokkedal-Lausch T, Plomgaard P, Nybo L, Larsen FJ, Cardinale DA, Jensen K, Holmberg HC, Vissing K & Ørtenblad N (2017). No superior adaptations to carbohydrate periodization in elite endurance athletes. Med Sci Sports Exerc 49, 2486-2497.
    1. Gomez-Bruton A, Gonzalez-Aguero A, Gomez-Cabello A, Casajus JA & Vicente-Rodriguez G (2013). Is bone tissue really affected by swimming? A systematic review. PLoS One 8, e70119.
    1. Gonzalez JT, Betts JA & Thompson D (2019). Carbohydrate availability as a regulator of energy balance with exercise. Exerc Sport Sci Rev, in press; .
    1. Hagmar M, Berglund B, Brismar K & Hirschberg AL (2013). Body composition and endocrine profile of male Olympic athletes striving for leanness. Clin J Sports Med 23, 197-201.
    1. Hammond KM, Impey SG, Currell K, Mitchell N, Shepherd SO, Jeromson S, Hawley JA, Close GL, Hamilton LD, Sharples AP & Morton JP (2016). Postexercise high-fat feeding suppresses p70S6K1 activity in human skeletal muscle. Med Sci Sport Exer 48, 2108.
    1. Hansen AK, Fischer CP, Plomgaard P, Andersen JL, Saltin B & Pedersen BK (2005). Skeletal muscle adaptation: training twice every second day vs. training once daily. J Appl Physiol 98, 93-99.
    1. Henriksen DB, Alexandersen P, Bjarnason NH, Vilsboll T, Hartmann B, Henriksen EE, Byrjalsen I, Krarup T, Holst JJ & Christiansen C (2003). Role of gastrointestinal hormones in postprandial reduction of bone resorption. J Bone Miner Res 18, 2180-2189.
    1. Holloway WR, Collier FM, Aitken CJ, Myers DE, Hodge JM, Malakellis M, Gough TJ, Collier GR & Nicholson GC (2002). Leptin inhibits osteoclast generation. J Bone Miner Res 17, 200-209.
    1. Horowitz JF, Mora-Rodriguez R, Byerley LO & Coyle EF (1997). Lipolytic suppression following carbohydrate ingestion limits fat oxidation during exercise. Am J Physiol Endocrin Metab 273, E768-E775.
    1. Hulston CJ, Venables MC, Mann CH, Martin C, Philp A, Baar K & Jeukendrup AE (2010). Training with low muscle glycogen enhances fat metabolism in well-trained cyclists. Med Sci Sports Exerc 42, 2046-2055.
    1. Ihle R & Loucks AB (2004). Dose-response relationships between energy availability and bone turnover in young exercising women. J Bone Miner Res 19, 1231-1240.
    1. Impey SG, Hammond KM, Shepherd SO, Sharples AP, Stewart C, Limb M, Smith K, Philp A, Jeromson S, Hamilton DL, Close GL & Morton JP (2016). Fuel for the work required: a practical approach to amalgamating train-low paradigms for endurance athletes. Phys Reports 4, e12803.
    1. Impey SG, Hearris MA, Hammond KM, Bartlett JD, Louis J, Close GL & Morton JP (2018). Fuel for the work required: a theoretical framework for carbohydrate periodization and the glycogen threshold hypothesis. J Sports Med 48, 1031-1048.
    1. Jensen MD, Ekberg K & Landau BR (2001). Lipid metabolism during fasting. Am J Physiol Endocrinol Metab 281, E789-E793.
    1. Jeukendrup AE & Wallis GA (2005). Measurement of substrate oxidation during exercise by means of gas exchange measurements. Int J Sports Med 1, 28-37.
    1. Keller C, Steensberg A, Pilegaard H, Osada T, Saltin B, Pedersen BK & Neufer PD (2001). Transcriptional activation of the IL-6 gene in human contracting skeletal muscle:influence of muscle glycogen content. FASEB J 15, 2748-2750.
    1. Kolaczynski JW, Considine RV, Ohannesian J, Marco C, Opentanova I, Nyce MR, Myint M & Caro JF (1996). Responses of leptin to short-term fasting and refeeding in humans: a link with ketogenesis but not ketones themselves. Diabetes 45, 1511-1515.
    1. Loucks AB, Verdun M & Heath EM (1998). Low energy availability, not stress of exercise, alters LH pulsatility in exercising women. J Appl Physiol 84, 37-46.
    1. Marquet LA, Brisswalter J, Louis J, Tiollier E, Burke LM, Hawley JA & Hausswirth C (2016). Enhanced endurance performance by periodization of CHO intake: “sleep low” strategy. Med Sci Sports Exerc 48, 663-672.
    1. Meynet O & Ricci JE (2014). Caloric restriction and cancer: molecular mechanisms and clinical implications. Trends Mol Med 20, 419-427.
    1. Morton JP, Croft L, Bartlett JD, Maclaren DPM, Reilly T, Evans L, McArdle A & Drust B (2009). Reduced carbohydrate availability does not modulate training-induced heat shock protein adaptations but does upregulated oxidative enzyme activity in human skeletal muscle. J Appl Physiol 106, 1513-1521.
    1. Mountjoy M, Sundgot-Borgen J, Burke LM, Carter S, Constantini N, Lebrun C, Meyer N, Sherman R, Steffen K, Budgett R & Ljungqvist A (2014). The IOC consensus statement: beyond the female athlete triad-relative energy deficiency in sport (RED-S). Br J Sports Med 48, 491-497.
    1. Nieman DC (2007). Marathon training and immune function. Sports Med 37, 412-415.
    1. Nieman DC, Davis JM, Henson DA, Walberg-Rankin J, Shute M, Dumke CL, Utter AC, Vinci DM, Carson JA, Brown A, Lee WJ, McAnulty SR & McAnulty LS (2003). Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. J Appl Physiol (1985) 94, 1917-1925.
    1. Nieman DC, Nehlsen-Cannarella SL, Fagoaga OR, Henson DA, Utter A, Davis JM, Williams F & Butterworth DE (1998). Influence of mode and carbohydrate on the cytokine response to heavy exertion. Med Sci Sports Exerc 30, 671-678.
    1. Olmedillas H, Gonzalez-Aguero A, Moreno LA, Casajus JA & Vicente-Rodriguez G (2012). Cycling and bone health: a systematic review. BMC Med 10, 168.
    1. Ozcivici E, Luu YK, Adler BA, Qin Y-X, Rubin J, Judex S & Rubin CT (2010). Mechanical signals as anabolic agents in bone. Nat Rev Rheumatol 6, 50-59.
    1. Pagnotti GM, Styner M, Uzer G, Patel VS, Wright LE, Ness KK, Guise TA, Rubin J & Rubin CT (2019). Combating osteoporosis and obesity with exercise: leveraging cell mechanosensitivity. Nat Rev Endocrinol 15, 339-355.
    1. Phillips T, Childs AC, Dreon DM, Phinney S & Leeuwenburgh C (2003). A dietary supplement attenuates IL-6 and CRP after eccentric exercise in untrained males. Med Sci Sports Exerc 35, 2032-2037
    1. Pilegaard H, Osada T, Andersen LT, Helge JW, Saltin B & Neufer PD (2005). Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise. Metab 54, 1048-1055.
    1. Psilander N, Frank P, Flockhart M & Sahlin K (2013). Exercise with low glycogen increases PGC-1α gene expression in human skeletal muscle. Eur J Appl Physiol 113, 951-963.
    1. Romijn JA, Coyle EF, Sidossis LS, Zhang XJ & Wolfe RR (1995). Relationship between fatty acid delivery and fatty acid oxidation during strenuous exercise. J Appl Physiol 79, 1939-1945.
    1. Sale C, Varley I, Jones TW, James RM, Tang JC, Fraser WD & Greeves JP (2015). Effect of carbohydrate feeding on the bone metabolic response to running. J Appl Physiol (1985) 119, 824-830.
    1. Schmittgen TD & Livak KJ (2008). Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3, 1101-1108.
    1. Scofield KL & Hecht S (2012). Bone health in endurance athletes: runners, cyclists, and swimmers. Curr Sports Med Rep 11, 328-334.
    1. Sidossis LS, Gastaldelli A, Klein, S & Wolfe RR (1997). Regulation of plasma fatty acid oxidation during low- and high-intensity exercise. Am J Physiol Endocrinol Metab 272, E1065-E1070.
    1. Steensberg A, Febbraio MA, Osada T, Schjerling P, van Hall G, Saltin B & Pedersen BK (2001). Interleukin-6 production in contracting human skeletal muscle is influenced by pre-exercise muscle glycogen content. J Physiol 537, 633-639.
    1. Stellingwerff T, Morton JP & Burke LM (2019). A framework for periodized nutrition for athletics. Int J Sports Nutr Exerc Metab 11, 1-29.
    1. Thomas DT, Erdman KA & Burke LM (2016). Position of the academy of nutrition and dietetics, dietitians of Canada, and the American College of sports medicine: nutrition and athletic performance. J Acad Nutr Diet 116, 501-528.
    1. Thomas T & Burguera B (2002). Is leptin the link between fat and bone mass? J Bone Miner Res 17, 1563-1569.
    1. Thompson, WR, Rubin CT & Rubin J (2012). Mechanical regulation of signalling pathways in bone. Gene 503, 179-193.
    1. Townsend R, Elliot-Sale KJ, Currell K, Tang J, Fraser WD & Sale C (2017). The effect of postexercise carbohydrate and protein ingestion on bone metabolism. Med Sci Sports Exerc 49, 1209-1218.
    1. van Loon LJ, Saris WH, Kruijshoop M & Wagenmakers AJ (2000). Maximizing postexercise muscle protein synthesis: carbohydrate supplementation and the application of amino acid or protein hydrolysate mixtures. Am J Clin Nutr 72, 106-110.
    1. Van Proeyen K, Szlufcik K, Nielens H, Ramaekers M & Hespel P (2011). Beneficial metabolic adaptations due to endurance exercise training in the fasted state. J Appl Physiol 110, 236-245.
    1. Vasikaran SD, Morris HA, Cooper C, Kanis JA (2011). Standardising biochemical assessment of bone turnover in osteoporosis. Clin Biochem 44, 1033-1034.
    1. Vogt S, Heinrich L, Schumacher YO, Grosshauser M, Blum A, Koing D, Berg A & Schmid A (2005). Energy intake and energy expenditure of elite cyclists during preseason training. Int J Sports Med 26, 701-706.
    1. Wilson G, Martin D, Morton JP & Close GL (2018). Male flat jockeys do not display deteriorations in bone density or resting metabolic rate in accordance with race riding experience: implications for RED-S. Int J Sport Nutr Exerc Metab 28, 434-439.
    1. Wright DC, Geiger PC, Han DH, Jones TE & Holloszy JO (2007). Calcium induces increases in peroxisome proliferator-activated receptor γ coactivator-1α and mitochondrial biogenesis by a pathway leading to p38 mitogen-activated protein kinase activation. J Biol Chem 282, 18793-18799.
    1. Yeo WK, Paton CD, Garnham AP, Burke LM, Carey AL & Hawley JA (2008). Skeletal muscle adaptation and performance responses to once a day versus twice every second day endurance training regimens. J Appl Physiol 105, 1462-1470.

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever