Abstract
Increased interleukin-6 (IL-6) plasma levels have been described to occur during physical exercise. A relative reduction in energy intake after physical activity has also been reported after exercise, indicating a possible involvement of IL-6 as an anorexigenic factor. Given the possible effect of interleukins on appetite, we assessed whether a controlled physical activity bout is related with changes in IL-6, IL-6 soluble receptor (IL-6sR), gp130 and interleukin-18 (IL-18) plasma levels, as well as their relation with post-exercise energy intake. A co-twin intervention study was carried out with five young male monozygotic twin pairs. One co-twin performed 45 min of submaximal exercise on a treadmill near the anaerobic threshold ending with 7 min at 90 % VO2 max, while his co-twin remained non-active. Ad libitum energy intake was tested through a carbohydrate-rich meal test. Venous blood samples were drawn at baseline, immediately after exercise and after the meal ingestion. Plasma concentrations of IL-6, IL-6sR, gp130 and IL-18 were measured via ELISA. IL-6 plasma levels increased after physical activity bout (2.6-fold change; p = 0.04). A less marked trend, although still significant, was observed for plasma levels of IL-6sR and gp130. Plasma levels of IL-18 did not significantly change during exercise. The twins who exercised exhibited significantly lower energy intake (181 versus 1,195 kcal; p = 0.04), compared to the co-twins who remained resting. The present study in monozygotic twins shows increased IL-6 plasma levels after acute physical exercise with a significant reduction in energy intake, supporting a linkage between IL-6 and acute post-exercise eating behaviour.
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References
American College of Sports Medicine (2001) Appropriate intervention strategies for weight loss and prevention of weight regain for adults. Med Sci Sports Exerc 33:2145–2156
Blundell JE (2006) Perspective on the central control appetite. Obes Res 14(Suppl):160S–163S
Blundell JE, Stubbs RJ, Hughes DA, Whybrow S, King NA (2003) Cross talk between physical activity and appetite control: does physical activity stimulate appetite? Proc Nutr Soc 62:651–661
Boomsma D, Busjahn A, Peltonen L (2002) Classical twin studies and beyond. Nat Rev Genet 3:872–882
Brooks GA (2001) Lactate doesn't necessarily cause fatigue: why are we surprised? J Physiol 536:1
Brooks GA (2009) Cell-cell and intracellular lactate shuttles. J Physiol 587:5591–5600
Broom DR, Batterham RL, King JA, Stensel DJ (2009) Influence of resistance and aerobic exercise on hunger, circulating levels of acylated ghrelin, and peptide YY in healthy males. Am J Physiol Regul Integr Comp Physiol 296:R29–R35
Bruun JM, Stallknecht B, Helge JW, Richelsen B (2007) Interleukin-18 in plasma and adipose tissue: effects of obesity, insulin resistance, and weight loss. Eur J Endocrinol 157:465–471
Carey AL, Steinberg GR, Macaulay SL, Thomas WG, Holmes AG et al (2006) IL-6 increases insulin stimulated glucose disposal in humans and glucose uptake and fatty acid oxidation in vitro via AMPK. Diabetes 55:2688–2697
Caudwell P, Gibbons C, Hopkins M, Naslund E, King N, Finlayson G, Blundell J (2011) The influence of physical activity on appetite control: an experimental system to understand the relationship between exercise-induced energy expenditure and energy intake. Proc Nutr Soc 70:171–180
Christian JC, Kang KW (1972) Efficiency of human monozygotic twins in studies of blood lipids. Metabolism 21:691–699
Cintra DE, Ropelle ER, Pauli JR (2007) Regulación central de la ingestión alimentaria y el gasto energético: acciones moleculares de la insulina, la leptina y el ejercicio físico. Rev Neurol 45:672–682
Coll AP, Farooqi S, O’Rahilli S (2007) The hormonal control of food intake. Cell 129:251–262
Cook CM, Schoeller DA (2011) Physical activity and weight control: conflicting findings. Clin Nutr Metab Care 14:419–424
Ellingsgaard H, Hauselmann I, Schuler B, Habib AM, Baggio LL et al (2011) Interleukin-6 enhances insulin secretion by increasing glucagon-like peptide-1 secretion from L cells and alpha cells. Nat Med 17:1481–1489
Febbraio MA, Pedersen BK (2002) Muscle-derived interleukin-6: mechanisms for activation and possible biological roles. FASEB J 16:1335–1347
Fisher CP (2006) Interleukin-6 in acute exercise and training: what is the biological relevance? Exerc Inmunol Rev 12:6–33
Flores MB, Fernandes MF, Ropelle ER, Faria MC, Ueno M, Velloso LA, Saad MJ, Carvalheira JB (2006) Exercise improves insulin and leptin sensitivity in hypothalamus of Wistar rats. Diabetes 55:2554–2561
Frayn K (2010) Metabolic regulation. A human perspective. Blackwell, Oxford
Gattas V (2008) Guía de la composición nutricional de alimentos naturales, de la industria y preparaciones Chilenas habituales. INTA-Universidad de Chile
Gray SR, Robinson M, Nimmo MA (2008) Response of plasma IL-6 and its soluble receptors during submaximal exercise to fatigue in sedentary middle-aged men. Cell Stress Chaperone 13:247–51
Gray SR, Clifford M, Lancaster R, Leggate M, Davies M, Nimmo MA (2009) The response of circulating levels of interlekin-6/interleukin-6 receptor complex to exercise in young men. Cytokine 47:98–102
Hall JG (2003) Twinning. Lancet 362:735–743
Heisler LK, Jobst EE, Sutton GM, Zhou L, Borok E, Thornton-Jones Z et al (2006) Serotonin reciprocally regulates melanocortin neurons to modulate food intake. Neuron 51:239–249
Hopkins M, King NA, Blundell JE (2010) Acute and long-term effects of exercise on appetite control: is there any benefit for weight control? Curr Opin Clin Nutr Metab Care 13:635–640
Jacobs BL, Fornal CA (1999) Activity of serotonergic neurons in behaving animals. Neuropsychopharmacology 21:9S–15S
Keller P, Keller C, Carey AL, Jauffred S, Fischer CP, Steensberg A, Pedersen BK (2003) Interleukin-6 production by contracting human skeletal muscle: autocrine regulation by IL-6. Biochem Biophys Res Commun 310:550–554
Kelly M, Keller C, Avilucea PR, Keller P, Luo Z, Xiang X, Giralt M, Hidalgo J, Saha AK, Pedersen BK (2004) AMPK activity is diminished in tissues of the IL-6 knockout mice: the effect of exercise. Biochem Biophys Res Commun 320:449–454
Kondo T, Nakae Y, Mitsui T, Kagaya M, Matsutani Y, Horibe H, Read NW (2001) Exercise-induced nausea is exaggerated by eating. Appetite 36:119–125
Kraemer RR, Chu H, Castracane VD (2002) Leptin and exercise. Exp Biol Med 227:701–708
Leibowitz SF, Alexander JT (1998) Hypothalamic serotonin in control of eating behavior, meal size, and body weight. Biol Psychiatry 44:851–864
Leick L, Lindegaard B, Stensvold D, Plomgaard P, Saltin B, Pilegaard H (2007) Adipose tissue interleukin-18 mRNA and plasma interleukin-18: effect of obesity and exercise. Obesity 15:356–363
Martínez de Morentin PB, López M (2010) "Mens sana in corpore sano": exercise and hypothalamic ER stress. PLoS Biol 8:e1000464
Martins C, Morgan LM, Bloom SR, Robertson MD (2007) Effect of exercise on gut peptides, energy intake and appetite. J Endocrinol 193:251–258
Martins C, Morgan L, Truby H (2008) A review of the effects of exercise on appetite regulation: an obesity perspective. Int J Obes 32:1337–1347
Martins C, Robertson MD, Morgan LM (2008) Effects of exercise and restrained eating behaviour on appetite control. Proc Nutr Soc 67:28–41
Melancon MO, Lorrain D, Dionne IJ (2011) Exercise increases tryptophan availability to the brain in older men age 57–70 years. Med Sci Sports Exerc 44:881–887
Moreno-Aliaga MJ, Pérez-Echarri N, Marcos-Gómez B, Larequi E, Gil-Bea FJ, Viollet B, Gimenez I, Martínez JA, Prieto J, Bustos M (2011) Cardiotrophin-1 is a key regulator of glucose and lipid metabolism. Cell Metab 14:242–253
Northoff H, Berg A (1991) Immunologic mediators as parameters of reaction to strenuous exercise. Int J Sports Med 12(suppl 1):S9–S15
Pedersen BK, Febbraio MA (2007) Point: interleukin-6 does have a beneficial role in insulin sensitivity and glucose homeostasis. J Appl Physiol 102:814–816
Pedersen BK, Fischer CP (2007) Beneficial health effects of exercise—the role of IL-6 as a myokine. Trends Pharmacol Sci 28:152–156
Pedersen BK, Fisher CP (2007) Physiological role of muscle-derived interleukin-6 in response to exercise. Clin Nutr Metab Care 10:265–271
Pedersen TH, Nielsen OB, Lamb GD, Stephenson DG (2004) Intracellular acidosis enhances the excitability of working muscle. Science 305:1144–1147
Perboni S, Inui A (2006) Anorexia in cancer: role of feeding-regulatory peptides. Phil Trans R Soc B 361:1281–1289
Peters M, Jacobs S, Ehlers M, Vollmer P, Mullberg J et al (1996) The function of soluble interleukin-6 receptor in vivo: sensitization of human soluble IL-6 receptor transgenic mice towards IL-6 and prolongation of plasma half-life of IL-6. J Exp Med 183:1399–406
Plata-Salaman CR (1996) Anorexia induced by activators of the signal transducer gp130. Neuroreport 7:841–844
Robergs RA, Ghiasvand F, Parker D (2004) Biochemistry of exercise-induced metabolic acidosis. Am J Physiol Regul Integr Comp Physiol 287:502–516
Robson-Ansley P, Barwood M, Canavan J, Hack S, Eglin C, Davey S, Hewitt J, Hull J, Ansley L (2009) The effect of repeated endurance exercise on IL-6 and sIL-6R and their relationship with sensations of fatigue rest. Cytokine 45:111–6
Robson-Ansley P, Cockburn E, Walshe I, Stevenson E, Nimmo M (2010) The effect of exercise on plasma soluble IL-6 receptor concentration: a dichotomous response. Exerc Immunol Rev 16:56–76
Ropelle ER, Fernandes MF, Flores MB, Ueno M, Rocco S, Marin R, Cintra DE, Velloso LA, Franchini KG, Saad MJ, Carvalheira JB (2008) Central exercise action increases the AMPK and mTOR response to leptin. PLoS One 3(12):e3856
Ropelle ER, Flores MB, Cintra DE, Rocha GZ, Pauli JR, Morari J, de Souza CT et al (2010) IL-6 and IL-10 anti-inflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKβ and ER stress inhibition. Plos Biol 8(8):e100046
Rose-John S (2003) Interleukin-6 biology is coordinated by membrane bound and soluble receptors. Acta Biochim Pol 50:603–11
Rueter LE, Jacobs BL (1996) A microdialysis examination of serotonin release in the rat forebrain induced by behavioral/environmental manipulations. Brain Res 739:57–69
Schuster B, Kovaleva M, Sun Y, Regenhard P, Matthews V, Grötzinger J, Rose-John S, Kallen KJ (2003) Signalling of human neurotrophic factor (CNTF) revisited. The interleukin-6 receptor can serve as an alpha-receptor for CTNF. J Biol Chem 278:9528–9535
Van Beaumont W (1972) Evaluation of hemoconcentration from hematocrit measurements. J Appl Physiol 32:712–713
Ward LD, Howlett GJ, Discolo G, Yasukawa K, Hammacher A, Moritz RL et al (1994) High affinity interleukin-6 receptor is a hexameric complex consisting of two molecules each of interleukin-6, interleukin-6 receptor and gp130. J Biol Chem 269:23286–23289
Wojtaszewski JF, Jorgensen SB, Frosig C, Macdonald C, Birk JB, Richter EA (2003) Insulin signalling: effects of prior exercise. Acta Physiol Scand 178:321–328
Young SN (2007) How to increase serotonin in the human brain without drugs. Psychiatry Neurosci 32:394–399
Zorrilla EP, Sanchez-Alavez M, Sugama S, Brennan M, Fernandez R, Bartfai T, Conti B (2007) Interleukin-18 controls energy homeostasis by suppressing appetite and feed efficiency. Proc Natl Acad Sci USA 104(26):11097–11102
Acknowledgments
This study was supported by a Chilean grant from the Fondo Nacional de Desarrollo Científico y Tecnológico 1090388. We acknowledge Dr. Fernando Yáñez, Francisca Márquez and María José Bustamante from the Medical Centre San Jorge (Pontificia Universidad Católica de Chile, Santiago, Chile) for their support. We are also grateful to M. Sc. Oscar Castillo for his collaboration.
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Almada, C., Cataldo, L.R., Smalley, S.V. et al. Plasma levels of interleukin-6 and interleukin-18 after an acute physical exercise: relation with post-exercise energy intake in twins. J Physiol Biochem 69, 85–95 (2013). https://doi.org/10.1007/s13105-012-0191-x
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DOI: https://doi.org/10.1007/s13105-012-0191-x