Microbiota influences host exercise capacity via modulation of skeletal muscle glucose metabolism in mice
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The microbiota enhances exercise performance and regulates host physiology and energy metabolism by producing beneficial metabolites via bacterial fermentation. In this study, we discovered that germ-free (GF) mice had a reduced capacity for aerobic exercise as well as low oxygen consumption rates and glucose availability. Surprisingly, GF mice showed lower body weight gain and lower fat mass than specific pathogen-free (SPF) mice. Therefore, we hypothesized that these paradoxical phenotypes could be mediated by a compensatory increase in lipolysis in adipose tissues owing to impaired glucose utilization in skeletal muscle. Our data revealed that gut microbiota depletion impairs host aerobic exercise capacity via the deterioration of glucose storage and utilization. The improved browning ability of GF mice may have contributed to the lean phenotype and negatively affected energy generation. These adaptations limit obesity in GF mice but impede their immediate fuel supply during exercise, resulting in decreased exercise performance.
Abstract
The microbiota enhances exercise performance and regulates host physiology and energy metabolism by producing beneficial metabolites via bacterial fermentation. In this study, we discovered that germ-free (GF) mice had a reduced capacity for aerobic exercise as well as low oxygen consumption rates and glucose availability. Surprisingly, GF mice showed lower body weight gain and lower fat mass than specific pathogen-free (SPF) mice. Therefore, we hypothesized that these paradoxical phenotypes could be mediated by a compensatory increase in lipolysis in adipose tissues owing to impaired glucose utilization in skeletal muscle. Our data revealed that gut microbiota depletion impairs host aerobic exercise capacity via the deterioration of glucose storage and utilization. The improved browning ability of GF mice may have contributed to the lean phenotype and negatively affected energy generation. These adaptations limit obesity in GF mice but impede their immediate fuel supply during exercise, resulting in decreased exercise performance.
참고문헌 (50)
- Hennis, P. J., "Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa : an observational study", Orphanet J Rare Dis, 17, pp.28~ (2022)
- Hargreaves, M., "Skeletal muscle energy metabolism during exercise", Nat. Metab, 2, pp.817~828 (2020)
- Joyner, M. J., "Endurance exercise performance : the physiology of champions", J. Physiol, 586, pp.35~44 (2008)
- Liu, Y., "Gut microbiome fermentation determines the efficacy of exercise for diabetes prevention", Cell Metab, 31, pp.77~ (2020)
- Okamoto, T., "Microbiome potentiates endurance exercise through intestinal acetate production", Am. J. Physiol. Endocrinol. Metabol, 316, pp.E956~E966 (2019)
- Dalton, A., "Exercise influence on the microbiome-gut-brain axis", Gut Microbes, 10, pp.555~568 (2019)
- Shiffer, A. M., "The exercise microbiome project : an 8 week cardiovascular intervention on the human gut microbiome", Med. Sci. Sports Exerc, 51, pp.866~866 (2019)
- Mailing, L. J., "Exercise and the gut microbiome : a review of the evidence, potential mechanisms, and implications for human health", Exerc. Sport Sci. Rev, 47, pp.75~85 (2019)
- Durk, R. P., "Gut microbiota composition is related to cardiorespiratory fitness in healthy young adults", Int. J. Sport Nutr. Exerc. Metab, 29, pp.249~253 (2019)
- Carey, R. A., "Exploring the relationship between gut microbiota and exercise : short-chain fatty acids and their role in metabolism", BMJ Open Sport Exerc. Med, 7, pp.e000930~ (2021)
- Frampton, J., "Short-chain fatty acids as potential regulators of skeletal muscle metabolism and function", Nat Metab, 2, pp.840~848 (2020)
- Matsumoto, M., "Voluntary running exercise alters microbiota composition and increases n-butyrate concentration in the rat cecum", Biosci. Biotechnol. Biochem, 72, pp.572~576 (2008)
- Koh, A., "From dietary fiber to host physiology : short-chain fatty acids as key bacterial metabolites", Cell, 165, pp.1332~1345 (2016)
- Allen, J. M., "Exercise alters gut microbiota composition and function in lean and obese humans", Med. Sci. Sports Exerc, 50, pp.747~757 (2018)
- Fromentin, S., "Microbiome and metabolome features of the cardiometabolic disease spectrum", Nat. Med, 28, pp.303~314 (2022)
- Mach, N., "Endurance exercise and gut microbiota : a review", J. Sport Health Sci, 6, pp.179~197 (2017)
- Hsu, Y. J., "Effect of intestinal microbiota on exercise performance in mice", J. Strength Cond. Res, 29, pp.552~558 (2015)
- Huang, W. C., "Investigation of the effects of microbiota on exercise physiological adaption, performance, and energy utilization using a gnotobiotic animal model", Front Microbiol, 10, pp.1906~ (2019)
- Backhed, F., "Mechanisms underlying the resistance to diet-induced obesity in germ-free mice", Proc. Natl. Acad Sci. USA, 104, pp.979~984 (2007)
- Suarez-Zamorano, N., "Microbiota depletion promotes browning of white adipose tissue and reduces obesity", Nat. Med, 21, pp.1497~1501 (2015)
- Rabot, S., "Germ-free C57BL", 6J mice are resistant to high-fat-diet-induced insulin resistance and have altered cholesterol metabolism, 2010, pp.24, 4948~4959
- Greiner, T., "Effects of the gut microbiota on obesity and glucose homeostasis", Trends Endocrin. Met, 22, pp.117~123 (2011)
- Kahn, B. B., "AMP-activated protein kinase : ancient energy gauge provides clues to modern understanding of metabolism", Cell Metab, 1, pp.15~25 (2005)
- Dougherty, J. P., "The treadmill fatigue test : a simple, high-throughput assay of fatigue-like behavior for the mouse", Jove-J. Vis. Exp, 111, pp.e54052~ (2016)
- Manca, C., "Germ-free mice exhibit profound gut microbiota-dependent alterations of intestinal endocannabinoidome signaling", J. Lipid Res, 61, pp.70~85 (2020)
- Maha Al-Asmakh, "Use of Germ-Free Animal Models in Microbiota-Related Research", Journal of Microbiology and Biotechnology, 25(10), pp.1583~1588 (2015), 한국미생물·생명공학회[DOI]
- Brooks, G. A., "The science and translation of lactate shuttle theory", Cell Metab, 27, pp.757~785 (2018)
- Wasserman, K., "The anaerobic threshold measurement to evaluate exercise performance", Am. Rev. Respir Dis, 129, pp.S35~S40 (1984)
- Takahashi, Y., "Enhanced skeletal muscle glycogen repletion after endurance exercise is associated with higher plasma insulin and skeletal muscle hexokinase 2 protein levels in mice : comparison of level running and downhill running model", J. Physiol. Biochem, 77, pp.469~480 (2021)
- Mackenzie, R. W. A, "Skeletal muscle glycogen synthesis-it turns out we still know very little", J. Physiol-London, 598, pp.5593~5594 (2020)
- Moretti, C. H., "Germ-free mice are not protected against diet-induced obesity and metabolic dysfunction", Acta Physiol, 231, pp.e13581~ (2021)
- Li, M., "Brown adipose tissue is the key depot for glucose clearance in microbiota depleted mice", Nat. Commun, 12, pp.4725~ (2021)
- Krisko, T. I., "Dissociation of adaptive thermogenesis from glucose homeostasis in microbiome-deficient mice", Cell Metab, 31, pp.592~ (2020)
- Schreiber, R., "Of mice and men : the physiological role of adipose triglyceride lipase(ATGL)", Bba-Mol. Cell Biol. L, 1864, pp.880~899 (2019)
- Kershaw, E. E., "Adipose triglyceride lipase-Function, regulation by insulin, and comparison with adiponutrin", Diabetes, 55, pp.148~157 (2006)
- Haemmerle, G., "Defective lipolysis and altered energy metabolism in mice lacking adipose triglyceride lipase", Science, 312, pp.734~737 (2006)
- Trites, M. J., "The role of adipose triglyceride lipase in lipid and glucose homeostasis : lessons from transgenic mice", Lipids Health Dis, 18, pp.204~ (2019)
- Hoy, A. J., "Adipose triglyceride lipase-null mice are resistant to high-fat dietinduced insulin resistance despite reduced energy expenditure and ectopic lipid accumulation", Endocrinology, 152, pp.48~58 (2011)
- Haedersdal, S., "The role of glucagon in the pathophysiology and treatment of type 2 diabetes", Mayo Clin. Proc, 93, pp.217~239 (2018)
- Martinez-Guryn, K., "Small intestine microbiota regulate host digestive and absorptive adaptive responses to dietary lipids", Cell Host Microbe, 23, pp.458~ (2018)
- Oliphant, K., "Macronutrient metabolism by the human gut microbiome : major fermentation by-products and their impact on host health", Microbiome, 7, pp.91~ (2019)
- Lundgren, P., "The microbiome-adipose tissue axis in systemic metabolism", Am. J. Physiol. Gastrointest. Liver Physiol, 318, pp.G717~G724 (2020)
- Kindt, A., "The gut microbiota promotes hepatic fatty acid desaturation and elongation in mice", Nat. Commun, 9, pp.3760~ (2018)
- Kim, H. J., "AMP-activated protein kinase activation in skeletal muscle modulates exercise-induced uncoupled protein 1 expression in brown adipocyte in mouse model", J Physiol, 600, pp.2359~2376 (2022)
- 김연주, "A comparison of the metabolic effects of treadmill and wheel running exercise in mouse model", Laboratory Animal Research, 36(1), pp.29~36 (2020), 한국실험동물학회[DOI]
- Yoshida, T., "Blood lactate parameters related to aerobic capacity and endurance performance", Eur. J. Appl. Physiol. Occup. Physiol, 56, pp.7~11 (1987)
- San-Millan, I., "Assessment of metabolic flexibility by means of measuring blood lactate, fat, and carbohydrate oxidation responses to exercise in professional endurance athletes and less-fit individuals", Sports Med, 48, pp.467~479 (2018)
- Irimia, J. M., "Impaired glucose tolerance and predisposition to the fasted state in liver glycogen synthase knock-out mice", J Biol. Chem, 285, pp.12851~12861 (2010)
- Takahashi, K., "Effects of post-exercise lactate administration on glycogen recovery in mouse skeletal muscle", Faseb. J, 34, pp.1~ (2020)
- Brooks, G. A., "Lactate production under fully aerobic conditions-the lactate shuttle during rest and exercise", Fed. Proc, 45, pp.2924~2929 (1986)
