Login Register Cart 0
Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Commentary

Exerkines: A Crosstalk between Lactate Production, Exercise and Mental Health

Author(s): Alberto Souza Sá Filho, Silvio Roberto Barsanulfo, Sara Socorro Faria, Pedro Augusto Inacio, Farahnaz Ayatizadeh and Sérgio Machado*

Volume 23, Issue 9, 2024

Published on: 12 October, 2023

Page: [1057 - 1060] Pages: 4

DOI: 10.2174/0118715273250928231009054658

Abstract

Muscle skeletal striated cells secrete a wide range of proteins called myokines or “exerkines”, which in turn perform autocrine, paracrine, or endocrine functions. For being able to act in the communication between skeletal muscle, adipose tissue, and mainly the brain, exerkines play a prominent role and potential influence on health promotion. Furthermore, we detected in the literature that one of these potential therapeutic substances derived from muscle contraction is a molecule derived from glycolytic metabolism that in the past was largely marginalized, the lactate. Currently, studies are dedicated to examining the target structures for exerkines that may contribute to the maintenance and restoration of mental health. Thus, lactate appears to be recognized as a critical mediator of exercise-related changes and their health benefits, particularly in their role in communication and coordination between organs. It is inferred that the BDNF expression mechanism can be induced by lactate, which in turn derives from the activation of SIRT pathways 1 and 2 and activates the PGC1-α cascade. The behavior of lactate concentration is intensity-dependent, directly related to the type of fast-twitch fibers (type IIb) and the recruitment of these fibers would potentiate the responses in the brain. In this sense, high-intensity exercise would establish itself as an important strategy to be considered. Despite this understanding, there is still much to be done. However, lactate appears to be a highly promising exerkine for future research initiatives and a potential biomarker to reduce illness and promote mental health.

Keywords: Myokines, biomarker, lactate, exercise, exerkines, mental health.

Next »
[1]
Cunnane SC, Trushina E, Morland C, et al. Brain energy rescue: An emerging therapeutic concept for neurodegenerative disorders of ageing. Nat Rev Drug Discov 2020; 19(9): 609-33.
[http://dx.doi.org/10.1038/s41573-020-0072-x] [PMID: 32709961]
[2]
Giudice J, Taylor JM. Muscle as a paracrine and endocrine organ. Curr Opin Pharmacol 2017; 34: 49-55.
[http://dx.doi.org/10.1016/j.coph.2017.05.005] [PMID: 28605657]
[3]
Karstoft K, Pedersen BK. Skeletal muscle as a gene regulatory endocrine organ. Curr Opin Clin Nutr Metab Care 2016; 19(4): 270-5.
[http://dx.doi.org/10.1097/MCO.0000000000000283] [PMID: 27101470]
[4]
Pedersen BK, Febbraio MA. Muscles, exercise and obesity: Skeletal muscle as a secretory organ. Nat Rev Endocrinol 2012; 8(8): 457-65.
[http://dx.doi.org/10.1038/nrendo.2012.49] [PMID: 22473333]
[5]
Pedersen BK. Physical activity and muscle–brain crosstalk. Nat Rev Endocrinol 2019; 15(7): 383-92.
[http://dx.doi.org/10.1038/s41574-019-0174-x] [PMID: 30837717]
[6]
Safdar A, Saleem A, Tarnopolsky MA. The potential of endurance exercise-derived exosomes to treat metabolic diseases. Nat Rev Endocrinol 2016; 12(9): 504-17.
[http://dx.doi.org/10.1038/nrendo.2016.76] [PMID: 27230949]
[7]
Ferguson BS, Rogatzki MJ, Goodwin ML, Kane DA, Rightmire Z, Gladden LB. Lactate metabolism: Historical context, prior misinterpretations, and current understanding. Eur J Appl Physiol 2018; 118(4): 691-728.
[http://dx.doi.org/10.1007/s00421-017-3795-6] [PMID: 29322250]
[8]
Raschke S, Eckel J. Adipo-myokines: Two sides of the same coin--mediators of inflammation and mediators of exercise. Mediators Inflamm 2013; 2013: 1-16.
[http://dx.doi.org/10.1155/2013/320724] [PMID: 23861558]
[9]
Wrann CD, White JP, Salogiannnis J, et al. Exercise induces hippocampal BDNF through a PGC-1α/FNDC5 pathway. Cell Metab 2013; 18(5): 649-59.
[http://dx.doi.org/10.1016/j.cmet.2013.09.008] [PMID: 24120943]
[10]
Pfanner N, Warscheid B, Wiedemann N. Mitochondrial proteins: From biogenesis to functional networks. Nat Rev Mol Cell Biol 2019; 20(5): 267-84.
[http://dx.doi.org/10.1038/s41580-018-0092-0] [PMID: 30626975]
[11]
Aladag T, Mogulkoc R, Baltaci AK. Irisin and energy metabolism and the role of irisin on metabolic syndrome. Mini Rev Med Chem 2023; 23(20): 1942-58.
[http://dx.doi.org/10.2174/1389557523666230411105506] [PMID: 37055896]
[12]
Waseem R, Shamsi A, Mohammad T, et al. FNDC5/Irisin: Physiology and pathophysiology. Molecules 2022; 27(3): 1118.
[http://dx.doi.org/10.3390/molecules27031118] [PMID: 35164383]
[13]
Lourenco MV, Frozza RL, de Freitas GB, et al. Exercise-linked FNDC5/irisin rescues synaptic plasticity and memory defects in Alzheimer’s models. Nat Med 2019; 25(1): 165-75.
[http://dx.doi.org/10.1038/s41591-018-0275-4] [PMID: 30617325]
[14]
Ballester-Ferrer JA, Roldan A, Cervelló E, Pastor D. Memory modulation by exercise in young adults is related to lactate and not affected by sex or BDNF polymorphism. Biology 2022; 11(10): 1541.
[http://dx.doi.org/10.3390/biology11101541] [PMID: 36290444]
[15]
Brooks GA, Osmond AD, Arevalo JA, et al. Lactate as a myokine and exerkine: Drivers and signals of physiology and metabolism. J Appl Physiol 2023; 134(3): 529-48.
[http://dx.doi.org/10.1152/japplphysiol.00497.2022]
[16]
Steensberg A, van Hall G, Osada T, Sacchetti M, Saltin B, Klarlund PB. Production of interleukin-6 in contracting human skeletal muscles can account for the exercise-induced increase in plasma interleukin-6. J Physiol 2000; 529(Pt 1): 237-42.
[http://dx.doi.org/10.1111/j.1469-7793.2000.00237.x]
[17]
Hojman P, Brolin C, Nørgaard-Christensen N, et al. IL-6 release from muscles during exercise is stimulated by lactate-dependent protease activity. Am J Physiol Endocrinol Metab 2019; 316(5): E940-7.
[http://dx.doi.org/10.1152/ajpendo.00414.2018] [PMID: 30779630]
[18]
Ting EYC, Yang AC, Tsai SJ. Role of interleukin-6 in depressive disorder. Int J Mol Sci 2020; 21(6): 2194.
[http://dx.doi.org/10.3390/ijms21062194] [PMID: 32235786]
[19]
Schiffer T, Schulte S, Sperlich B, Achtzehn S, Fricke H, Strüder HK. Lactate infusion at rest increases BDNF blood concentration in humans. Neurosci Lett 2011; 488(3): 234-7.
[http://dx.doi.org/10.1016/j.neulet.2010.11.035] [PMID: 21094220]
[20]
Autry AE, Monteggia LM. Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 2012; 64(2): 238-58.
[http://dx.doi.org/10.1124/pr.111.005108] [PMID: 22407616]
[21]
de Sá AS, Campos C, Rocha NB, et al. Neurobiology of bipolar disorder: Abnormalities on cognitive and cortical functioning and biomarker levels. CNS Neurol Disord Drug Targets 2016; 15(6): 713-22.
[http://dx.doi.org/10.2174/1871527315666160321111359] [PMID: 26996165]
[22]
Sá Filho AS, Cheniaux E, de Paula CC, et al. Exercise is medicine: A new perspective for health promotion in bipolar disorder. Expert Rev Neurother 2020; 20(11): 1099-107.
[http://dx.doi.org/10.1080/14737175.2020.1807329] [PMID: 32762382]
[23]
Gomez-Pinilla F, Vaynman S, Ying Z. Brain-derived neurotrophic factor functions as a metabotrophin to mediate the effects of exercise on cognition. Eur J Neurosci 2008; 28(11): 2278-87.
[http://dx.doi.org/10.1111/j.1460-9568.2008.06524.x] [PMID: 19046371]
[24]
Seifert T, Brassard P, Wissenberg M, et al. Endurance training enhances BDNF release from the human brain. Am J Physiol Regul Integr Comp Physiol 2010; 298(2): R372-7.
[http://dx.doi.org/10.1152/ajpregu.00525.2009] [PMID: 19923361]
[25]
Saucedo Marquez CM, Vanaudenaerde B, Troosters T, Wenderoth N. High-intensity interval training evokes larger serum BDNF levels compared with intense continuous exercise. J Appl Physiol 2015; 119(12): 1363-73.
[26]
El Hayek L, Khalifeh M, Zibara V, et al. Lactate mediates the effects of exercise on learning and memory through SIRT1-dependent activation of hippocampal brain-derived neurotrophic factor (BDNF). J Neurosci 2019; 39(13): 1661-8.
[http://dx.doi.org/10.1523/JNEUROSCI.1661-18.2019] [PMID: 30692222]
[27]
Gundersen V, Storm-Mathisen J, Bergersen LH. Neuroglial transmission. Physiol Rev 2015; 95(3): 695-726.
[http://dx.doi.org/10.1152/physrev.00024.2014] [PMID: 26084688]
[28]
Finkbeiner S, Tavazoie SF, Maloratsky A, Jacobs KM, Harris KM, Greenberg ME. CREB: A major mediator of neuronal neurotrophin responses. Neuron 1997; 19(5): 1031-47.
[http://dx.doi.org/10.1016/S0896-6273(00)80395-5] [PMID: 9390517]
[29]
Yang J, Ruchti E, Petit JM, et al. Lactate promotes plasticity gene expression by potentiating NMDA signaling in neurons. Proc Natl Acad Sci 2014; 111(33): 12228-33.
[http://dx.doi.org/10.1073/pnas.1322912111] [PMID: 25071212]
[30]
Carrard A, Elsayed M, Margineanu M, et al. Peripheral administration of lactate produces antidepressant-like effects. Mol Psychiatry 2018; 23(2): 392-9.
[http://dx.doi.org/10.1038/mp.2016.179] [PMID: 27752076]
[31]
Margineanu MB, Mahmood H, Fiumelli H, Magistretti PJ. L-lactate regulates the expression of synaptic plasticity and neuroprotection genes in cortical neurons: A transcriptome analysis. Front Mol Neurosci 2018; 11: 375.
[http://dx.doi.org/10.3389/fnmol.2018.00375] [PMID: 30364173]
[32]
Liu Y, Cox SR, Morita T, Kourembanas S. Hypoxia regulates vascular endothelial growth factor gene expression in endothelial cells. Identification of a 5′ enhancer. Circ Res 1995; 77(3): 638-43.
[http://dx.doi.org/10.1161/01.RES.77.3.638] [PMID: 7641334]
[33]
Hunt TK, Aslam RS, Beckert S, et al. Aerobically derived lactate stimulates revascularization and tissue repair via redox mechanisms. Antioxid Redox Signal 2007; 9(8): 1115-24.
[http://dx.doi.org/10.1089/ars.2007.1674] [PMID: 17567242]

Rights & Permissions Print Cite
Article Metrics
36
© 2024 Bentham Science Publishers | Privacy Policy