An arginine, alanine, and phenylalanine mixture increases synthesis of ketone bodies during low-intensity exercise via stimulating glucagon secretion in men with obesity
During exercise, levels of several hormones are acutely increased in the blood. We previously reported that pre-exercise ingestion of a specific combination of amino acids (arginine, alanine, and phenylalanine; A-mix) increases fat mobilization and ketone body synthesis by increasing secretion of ad...
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| Published in | The Journal of Physical Fitness and Sports Medicine Vol. 6; no. 5; pp. 325 - 333 |
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| Main Authors | , , |
| Format | Journal Article |
| Language | English |
| Published |
The Japanese Society of Physical Fitness and Sports Medicine
25.09.2017
Japanese Society of Physical Fitness and Sports Medicine |
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| ISSN | 2186-8131 2186-8123 2186-8123 |
| DOI | 10.7600/jpfsm.6.325 |
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| Abstract | During exercise, levels of several hormones are acutely increased in the blood. We previously reported that pre-exercise ingestion of a specific combination of amino acids (arginine, alanine, and phenylalanine; A-mix) increases fat mobilization and ketone body synthesis by increasing secretion of adrenalin and glucagon in healthy active young men. Herein, we sought to determine whether this acute hormone response could be induced upon administration of A-mix combined with exercise in patients with obesity during periods of low-intensity exercise. We performed a randomized crossover study of eleven middle-aged men with obesity without regular exercise habits, administered either A-mix (3 g/dose) or a placebo (3 g of dextrin/dose). Thirty minutes after ingestion, each subject subsequently performed workload tests on a cycle ergometer at 40% of peak oxygen consumption for 1 h. Following oral intake of A-mix, the concentration of plasma ketone bodies was significantly increased during exercise. This was accompanied by a significant increase in the area under the concentration-time curve for glucagon. Taken together, these results indicate that pre-exercise ingestion of the A-mix supplement significantly accelerated hepatic ketone body synthesis via stimulation of glucagon secretion during exercise in men with obesity. |
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| AbstractList | During exercise, levels of several hormones are acutely increased in the blood. We previously reported that pre-exercise ingestion of a specific combination of amino acids (arginine, alanine, and phenylalanine; A-mix) increases fat mobilization and ketone body synthesis by increasing secretion of adrenalin and glucagon in healthy active young men. Herein, we sought to determine whether this acute hormone response could be induced upon administration of A-mix combined with exercise in patients with obesity during periods of low-intensity exercise. We performed a randomized crossover study of eleven middle-aged men with obesity without regular exercise habits, administered either A-mix (3 g/dose) or a placebo (3 g of dextrin/dose). Thirty minutes after ingestion, each subject subsequently performed workload tests on a cycle ergometer at 40% of peak oxygen consumption for 1 h. Following oral intake of A-mix, the concentration of plasma ketone bodies was significantly increased during exercise. This was accompanied by a significant increase in the area under the concentration-time curve for glucagon. Taken together, these results indicate that pre-exercise ingestion of the A-mix supplement significantly accelerated hepatic ketone body synthesis via stimulation of glucagon secretion during exercise in men with obesity. |
| Author | Ikegami, Shuji Sanbongi, Chiaki Ueda, Keisuke |
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| References | 21) Gore CJ, Booth ML, Bauman A and Owen N. 1999. Utility of pwc75% as an estimate of aerobic power in epidemiological and population-based studies. Med Sci Sports Exerc 31: 348-351. 8) Miyashita M. 2008. Effects of continuous versus accumulated activity patterns on postprandial triacylglycerol concentrations in obese men. Int J Obes 32: 1271-1278. doi: 10.1038/ijo.2008.73. 1) Batsis JA, Nieto-Martinez RE and Lopez-Jimenez F. 2007. Metabolic syndrome: from global epidemiology to individualized medicine. Clin Pharmacol Ther 82: 509-524. doi: 10.1038/sj.clpt.6100355. 14) Billington CJ, Bartness TJ, Briggs J, Levine AS and Morely JE. 1987. Glucagon stimulation of brown adipose tissue growth and thermogenesis. Am J Physiol 252: R160-R165. 25) McMurray RG, Forsythe WA, Mar MH and Hardy CJ. 1987. Exercise intensity-related responses of beta-endorphin and catecholamines. Med Sci Sports Exerc 19: 570-574. 23) Wasserman DH, Spalding JA, Lacy DB, Colburn CA, Goldstein RE and Cherringon AD. 1989. Glucagon is a primary controller of hepatic glycogenolysis and gluconeogenesis during muscular work. Am J Physiol 257: E108-E117. 20) Ministry of Health, Labour and Welfare. Report on National Health and Nutrition Survey 2015. Available from: http://www.mhlw.go.jp/bunya/kenkou/eiyou/dl/h27-houkoku.pdf. Accessed March 27, 2017. 22) McGarry JD and Foster DW. 1980. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49: 395-420. doi: 10.1146/annurev.bi.49.070180.002143. 19) Dériaz O, Dumont M, Bergeron N, Després JP, Brochu M and Prud’homme D. 2001. Skeletal muscle low attenuation area and maximal fat oxidation rate during submaximal exercise in male obese individuals. Int J Obes Relat Metab Disord 25: 1579-1584. doi: 10.1038/sj.ijo.0801809. 13) Tan TM, Field BC, McCullough KA, Troke RC, Chambers ES, Salem V, Gonzalez Maffe J, Baynes KC, De Silva A, Viardot A, Alsafi A, Frost GS, Ghatei MA and Bloom SR. 2013. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes 62: 1131-1138. doi: 10.2337/db12-0797. 2) Zou C and Shao J. 2008. Role of adipocytokines in obesity-associated insulin resistance. J Nutr Biochem 19: 277-286. doi: 10.1016/j.jnutbio.2007.06.006. 26) Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E and Wolfe RR. 1993. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol 265 (Pt 1): E380-E391. 3) Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE, Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM, Yanovski SZ and Jordan HS et al. 2013. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129: S102-S138. doi: 10.1161/01.cir.0000437739.71477.ee. 15) Suzuki T, Morita M, Hayashi T and Kamimura A. 2017. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males. Biosci Biotechnol Biochem 81: 372-375. doi: 10.1080/09168451.2016.1230007. 18) Ueda K, Sanbongi C, Takai S, Ikegami S and Fujita S. 2017. Combination of aerobic exercise and an arginine, alanine, and phenylalanine mixture increases fat mobilization and ketone body synthesis. Biosci Biotechnol Biochem 81: 1417-1424. doi: 10.1080/09168451.2017.1303359. 17) Shi W, Meininger CJ, Haynes TE, Hatakeyama K and Wu G. 2004. Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells. Cell Biochem Biophys 41: 415-434. 5) Mitchell HW, Peter HB, Robert MO and Lawrence EA. 2006. American College of Sports Medicine: clinical exercise testing. In ACSM’s guidelines for exercise testing and prescription (7th edition) (Whaley MH eds.): 93-114. 6) Richter EA, Kiens B, Mizuno M and Strange S. 1989. Insulin action in human thighs after one-legged immobilization. J Appl Physiol 67: 19-23. 9) Saunders TJ, Palombella A, McGuire KA, Janiszewski PM, Després JP and Ross R. 2012. Acute exercise increases adiponectin levels in abdominally obese men. J Nutr Metab 2012: 148729. doi: 10.1155/2012/148729. 24) Wolfe RR, Nadel ER, Shaw JH, Stephenson LA and Wolfe MH. 1986. Role of changes in insulin and glucagon in glucose homeostasis in exercise. J Clin Invest 77: 900-907. doi: 10.1172/JCI112388. 10) Gannon MC and Nuttall FQ. 2010. Amino acid ingestion and glucose metabolism - a review. IUBMB Life 62: 660-668. doi: 10.1002/iub.375. 16) Shinozaki F and Abe T. 2008. Synergistic effect of vespa amino acid mixture on lipolysis in rat adipocytes. Biosci Biotechnol Biochem 72: 1860-1868. 4) Jakicic JM. 2003. Exercise in the treatment of obesity. Endocrinol Metab Clin North Am 32: 967-980. 7) Numao S, Hayashi Y, Katayama Y, Matsuo T, Tomita T, Ohkawara K, Nakata Y and Tanaka K. 2006. Effects of obesity phenotype on fat metabolism in obese men during endurance exercise. Int J Obes 30: 1189-1196. doi: 10.1038/sj.ijo.0803282. 11) Wasserman DH, Williames PE, Lacy DB, Green DR and Cherrington AD. 1988. Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery. Am J Physiol 254: E518-E525. 12) Wolfe RR, Nadel ER, Shaw JHF, Stephenson LA and Wolfe MH. 1986. Role of changes in insulin and glucagon in glucose homeostasis in exercise. J Clin Invest 77: 900-907. doi: 10.1172/JCI112388. 22 23 24 25 26 10 11 12 13 14 15 16 17 18 19 1 2 3 4 5 6 7 8 9 20 21 |
| References_xml | – reference: 15) Suzuki T, Morita M, Hayashi T and Kamimura A. 2017. The effects on plasma L-arginine levels of combined oral L-citrulline and L-arginine supplementation in healthy males. Biosci Biotechnol Biochem 81: 372-375. doi: 10.1080/09168451.2016.1230007. – reference: 5) Mitchell HW, Peter HB, Robert MO and Lawrence EA. 2006. American College of Sports Medicine: clinical exercise testing. In ACSM’s guidelines for exercise testing and prescription (7th edition) (Whaley MH eds.): 93-114. – reference: 6) Richter EA, Kiens B, Mizuno M and Strange S. 1989. Insulin action in human thighs after one-legged immobilization. J Appl Physiol 67: 19-23. – reference: 17) Shi W, Meininger CJ, Haynes TE, Hatakeyama K and Wu G. 2004. Regulation of tetrahydrobiopterin synthesis and bioavailability in endothelial cells. Cell Biochem Biophys 41: 415-434. – reference: 21) Gore CJ, Booth ML, Bauman A and Owen N. 1999. Utility of pwc75% as an estimate of aerobic power in epidemiological and population-based studies. Med Sci Sports Exerc 31: 348-351. – reference: 23) Wasserman DH, Spalding JA, Lacy DB, Colburn CA, Goldstein RE and Cherringon AD. 1989. Glucagon is a primary controller of hepatic glycogenolysis and gluconeogenesis during muscular work. Am J Physiol 257: E108-E117. – reference: 12) Wolfe RR, Nadel ER, Shaw JHF, Stephenson LA and Wolfe MH. 1986. Role of changes in insulin and glucagon in glucose homeostasis in exercise. J Clin Invest 77: 900-907. doi: 10.1172/JCI112388. – reference: 24) Wolfe RR, Nadel ER, Shaw JH, Stephenson LA and Wolfe MH. 1986. Role of changes in insulin and glucagon in glucose homeostasis in exercise. J Clin Invest 77: 900-907. doi: 10.1172/JCI112388. – reference: 2) Zou C and Shao J. 2008. Role of adipocytokines in obesity-associated insulin resistance. J Nutr Biochem 19: 277-286. doi: 10.1016/j.jnutbio.2007.06.006. – reference: 20) Ministry of Health, Labour and Welfare. Report on National Health and Nutrition Survey 2015. Available from: http://www.mhlw.go.jp/bunya/kenkou/eiyou/dl/h27-houkoku.pdf. Accessed March 27, 2017. – reference: 25) McMurray RG, Forsythe WA, Mar MH and Hardy CJ. 1987. Exercise intensity-related responses of beta-endorphin and catecholamines. Med Sci Sports Exerc 19: 570-574. – reference: 13) Tan TM, Field BC, McCullough KA, Troke RC, Chambers ES, Salem V, Gonzalez Maffe J, Baynes KC, De Silva A, Viardot A, Alsafi A, Frost GS, Ghatei MA and Bloom SR. 2013. Coadministration of glucagon-like peptide-1 during glucagon infusion in humans results in increased energy expenditure and amelioration of hyperglycemia. Diabetes 62: 1131-1138. doi: 10.2337/db12-0797. – reference: 26) Romijn JA, Coyle EF, Sidossis LS, Gastaldelli A, Horowitz JF, Endert E and Wolfe RR. 1993. Regulation of endogenous fat and carbohydrate metabolism in relation to exercise intensity and duration. Am J Physiol 265 (Pt 1): E380-E391. – reference: 1) Batsis JA, Nieto-Martinez RE and Lopez-Jimenez F. 2007. Metabolic syndrome: from global epidemiology to individualized medicine. Clin Pharmacol Ther 82: 509-524. doi: 10.1038/sj.clpt.6100355. – reference: 7) Numao S, Hayashi Y, Katayama Y, Matsuo T, Tomita T, Ohkawara K, Nakata Y and Tanaka K. 2006. Effects of obesity phenotype on fat metabolism in obese men during endurance exercise. Int J Obes 30: 1189-1196. doi: 10.1038/sj.ijo.0803282. – reference: 19) Dériaz O, Dumont M, Bergeron N, Després JP, Brochu M and Prud’homme D. 2001. Skeletal muscle low attenuation area and maximal fat oxidation rate during submaximal exercise in male obese individuals. Int J Obes Relat Metab Disord 25: 1579-1584. doi: 10.1038/sj.ijo.0801809. – reference: 3) Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, Hu FB, Hubbard VS, Jakicic JM, Kushner RF, Loria CM, Millen BE, Nonas CA, Pi-Sunyer FX, Stevens J, Stevens VJ, Wadden TA, Wolfe BM, Yanovski SZ and Jordan HS et al. 2013. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation 129: S102-S138. doi: 10.1161/01.cir.0000437739.71477.ee. – reference: 18) Ueda K, Sanbongi C, Takai S, Ikegami S and Fujita S. 2017. Combination of aerobic exercise and an arginine, alanine, and phenylalanine mixture increases fat mobilization and ketone body synthesis. Biosci Biotechnol Biochem 81: 1417-1424. doi: 10.1080/09168451.2017.1303359. – reference: 22) McGarry JD and Foster DW. 1980. Regulation of hepatic fatty acid oxidation and ketone body production. Annu Rev Biochem 49: 395-420. doi: 10.1146/annurev.bi.49.070180.002143. – reference: 10) Gannon MC and Nuttall FQ. 2010. Amino acid ingestion and glucose metabolism - a review. IUBMB Life 62: 660-668. doi: 10.1002/iub.375. – reference: 4) Jakicic JM. 2003. Exercise in the treatment of obesity. Endocrinol Metab Clin North Am 32: 967-980. – reference: 14) Billington CJ, Bartness TJ, Briggs J, Levine AS and Morely JE. 1987. Glucagon stimulation of brown adipose tissue growth and thermogenesis. Am J Physiol 252: R160-R165. – reference: 16) Shinozaki F and Abe T. 2008. Synergistic effect of vespa amino acid mixture on lipolysis in rat adipocytes. Biosci Biotechnol Biochem 72: 1860-1868. – reference: 11) Wasserman DH, Williames PE, Lacy DB, Green DR and Cherrington AD. 1988. Importance of intrahepatic mechanisms to gluconeogenesis from alanine during exercise and recovery. Am J Physiol 254: E518-E525. – reference: 9) Saunders TJ, Palombella A, McGuire KA, Janiszewski PM, Després JP and Ross R. 2012. Acute exercise increases adiponectin levels in abdominally obese men. J Nutr Metab 2012: 148729. doi: 10.1155/2012/148729. – reference: 8) Miyashita M. 2008. Effects of continuous versus accumulated activity patterns on postprandial triacylglycerol concentrations in obese men. Int J Obes 32: 1271-1278. doi: 10.1038/ijo.2008.73. – ident: 23 doi: 10.1152/ajpendo.1989.257.1.E108 – ident: 26 doi: 10.1152/ajpendo.1993.265.3.E380 – ident: 14 doi: 10.1152/ajpregu.1987.252.1.R160 – ident: 9 doi: 10.1155/2012/148729 – ident: 1 doi: 10.1038/sj.clpt.6100355 – ident: 2 doi: 10.1016/j.jnutbio.2007.06.006 – ident: 16 doi: 10.1271/bbb.80119 – ident: 7 doi: 10.1038/sj.ijo.0803282 – ident: 17 doi: 10.1385/CBB:41:3:415 – ident: 13 doi: 10.2337/db12-0797 – ident: 20 – ident: 22 doi: 10.1146/annurev.bi.49.070180.002143 – ident: 25 doi: 10.1249/00005768-198712000-00005 – ident: 5 – ident: 11 doi: 10.1152/ajpendo.1988.254.4.E518 – ident: 24 doi: 10.1172/JCI112388 – ident: 3 doi: 10.1161/01.cir.0000437739.71477.ee – ident: 19 doi: 10.1038/sj.ijo.0801809 – ident: 6 doi: 10.1152/jappl.1989.67.1.19 – ident: 8 doi: 10.1038/ijo.2008.73 – ident: 21 doi: 10.1097/00005768-199902000-00020 – ident: 12 doi: 10.1172/JCI112388 – ident: 10 doi: 10.1002/iub.375 – ident: 4 doi: 10.1016/S0889-8529(03)00075-6 – ident: 15 doi: 10.1080/09168451.2016.1230007 – ident: 18 doi: 10.1080/09168451.2017.1303359 |
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| Title | An arginine, alanine, and phenylalanine mixture increases synthesis of ketone bodies during low-intensity exercise via stimulating glucagon secretion in men with obesity |
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