МИОКИН ИРИСИН – МОЛЕКУЛЯРНЫЙ СИГНАЛ, ОПОСРЕДУЮЩИЙ БЛАГОТВОРНОЕ ВЛИЯНИЕ ФИЗИЧЕСКОЙ АКТИВНОСТИ НА ФУНКЦИИ МОЗГА И ЦИРКАДИАННУЮ СИСТЕМУ (ОБЗОР)
Аннотация
Цель: обзор современных данных о центральной активности миокина ирисина. Методы исследования. Использован теоретический анализ научных публикаций за период 2010–2023 гг. по проблеме физиологической роли ирисина в опосредовании благотворного влияния физической активности на функции мозга и циркадианную систему. Результаты. Миокин ирисин, открытый в 2012 г., является продуктом расщепления фибронектин тип III домен-содержащего протеина (FNDC5). Ирисин продуцируется в скелетных мышцах при их сокращениях, выделяется в системный кровоток и оказывает ряд периферических эффектов, наиболее известным среди которых является стимуляция превращения клеток белой жировой ткани в бурые адипоциты. Кроме этого, ирисин способен проникать сквозь гематоэнцефалический барьер и оказывать центральное действие, являясь химическим посредником благотворного влияния физической активности на функции мозга. Ирисин, являющийся сигнальной молекулой в рамках функциональной оси «мышцы – мозг», проявляет набор положительных центральных эффектов в норме и при патологии, что выражается в улучшении когнитивных функций, психического состояния, синаптической пластичности и памяти, замедлении развития нейродегенеративных заболеваний и нейропротекторном действии. В циркадианной системе ирисин непосредственно участвует в механизмах синхронизации биологических часов супрахиазматического ядра в соответствии с уровнем физической активности. Получены данные о том, что рецептором ирисина в жировой и костной ткани является интегрин αVβ5, однако рецепторы ирисина в ЦНС до сих пор не идентифицированы, что существенно затрудняет исследование механизмов его центральной активности. Центральная активность ирисина может быть в определенной степени обусловлена его способностью стимулировать экспрессию мозгового нейротрофического фактора BDNF. Получены данные о том, что BDNF играет ключевую роль в фотической настройке циркадианных часов супрахиазматического ядра, опосредуя фазовые сдвиги ритма.
Литература
2. Радугин Ф.М., Тимкина Н.В., Каронова Т.Л. Метаболические свойства ирисина в норме и при сахарном диабете // Ожирение и метаболизм. 2022. Т. 19, № 3. С. 332–339. [Radugin F.M., Timkina N.V., Karonova T.L. [Metabolic Properties of Irisin in Health and in Diabetes Mellitus]. Ozhirenie i metabolizm [Obesity and Metabolism], 2022, vol. 19, no. 3, pp. 332–339. (in Russ.)] DOI: 10.14341/omet12899
3. Smith P.J., Blumenthal J.A., Hoffman B.M. et al. Aerobic Exercise and Neurocognitive Performance: A Meta-Analytic Review of Randomized Controlled Trials. Psychosomatic Medicine, 2010, vol. 72, pp. 239–252. DOI: 10.1097/PSY.0b013e3181d14633
4. Bostrom P., Wu J., Jedrychowski M.P. et al. A PGC1α-Dependent Myokine that Drives Browning of White Fat and Thermogenesis. Nature, 2012, vol. 481, pp. 463–468. DOI: 10.1038/nature10777
5. Ashton A., Foster R.G., Jagannath A. Photic Entrainment of the Circadian System. International Journal of Molecular Sciences, 2022, vol. 23, art. 729. DOI: 10.3390/ijms23020729
6. Zsuga J., More C.E., Erdei T. et al. Blind Spot for Sedentarism: Redefining the Diseasome of Physical Inactivity in View of Circadian System and the Irisin/BDNF Axis. Frontiers in Neurology, 2018, vol. 9, art. 818. DOI: 10.3389/fneur.2018.00818
7. Oguri Y., Shinoda K., Kim H. et al. CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling. Cell, 2020, vol. 182, pp. 563–577. DOI: 10.1016/j.cell.2020.06.021
8. Bilu C., Frolinger-Ashkenazi T., Einat H. et al. Effects of Photoperiod and Diet on BDNF Daily Rhythms in Diurnal Sand Rats. Behavioural Brain Research, 2022, vol. 418, art. 113666. DOI: 10.1016/j.bbr.2021.113666
9. Islam M.R., Valaris S., Young M.F. et al. Exercise Hormone Irisin is a Critical Regulator of Cognitive Function. Nature Metabolism, 2021, vol. 3, pp. 1058–1070. DOI: 10.1038/s42255-021-00438-z
10. Lourenco M.V., Frozza R.L., de Freitas G.B. et al. Exercise-Linked FNDC5/Irisin Rescues Synaptic Plasticity and Memory Defects in Alzheimer’s Models. Nature Medicine, 2019, vol. 25, pp. 165–175. DOI: 10.1038/s41591-018-0275-4
11. Waseem R., Shamsi A., Mohammad T. et al. FNDC5/Irisin: Physiology and Pathophysiology. Molecules, 2022, vol. 27, art. 1118. DOI: 10.3390/molecules27031118
12. Hastings M.H., Brancaccio M., Maywood E.S. Circadian Pacemaking in Cells and Circuits of the Suprachiasmatic Nucleus. Journal of Neuroendocrinology, 2014, vol. 26, pp. 2–10. DOI: 10.1111/jne.12125
13. Hastings M.H., Maywood E.S., Brancaccio M. Generation of Circadian Rhythms in the Suprachiasmatic Nucleus. Nature Reviews Neuroscience, 2018, vol. 19, pp. 453–469. DOI: 10.1038/s41583-018-0026-z
14. Zhang W., Chang L., Zhang C. et al. Irisin: a Myokine with Locomotor Activity. Neuroscience Letters, 2015, vol. 595, pp. 7–11. DOI: 10.1016/j.neulet.2015.03.069
15. Estell E.G., Le P.T., Vegting Y. et al. Irisin Directly Stimulates Osteoclastogenesis and Bone Resorption In Vitro and In Vivo. eLife, 2020, vol. 9, art. e58172. DOI: 10.7554/eLife.58172
16. Qiao X., Nie Y., Ma Y. et al. Irisin Promotes Osteoblast Proliferation and Differentiation via Activating the MAP Kinase Signaling Pathways. Scientific Reports, 2016, vol. 6, art. 18732. DOI: 10.1038/srep18732
17. Bi J., Zhang J., Ren Y. et al. Irisin Reverses Intestinal Epithelial Barrier Dysfunction During Intestinal Injury via Binding to the Integrin αVβ5 Receptor. Journal of Cellular and Molecular Medicine, 2020, vol. 24, pp. 996–1009. DOI: 10.1111/jcmm.14811
18. Zhang Y., Li R., Meng Y. et al. Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling. Diabetes, 2014, vol. 63, pp. 514–525. DOI: 10.2337/db13-1106
19. Jodeiri Farshbaf M., Alvina K. Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin. Frontiers in Aging Neuroscience, 2021, vol. 13, art. 649929. DOI: 10.3389/fnagi.2021.649929
20. Mendoza G., Merchant H. Motor System Evolution and the Emergence of High Cognitive Functions. Progress in Neurobiology, 2014, vol. 122, pp. 73–93. DOI: 10.1016/j.pneurobio.2014.09.001
21. Rabiee F., Lachinani L., Ghaedi S. et al. New Insights into the Cellular Activities of Fndc5/Irisin and its Signaling Pathways. Cell & Bioscience, 2020, vol. 10, art. 51. DOI: 10.1186/s13578-020-00413-3
22. Park H., Poo M.M. Neuroprophin Regulation of Neural Circuit Development and Function. Nature Review Neurocsience, 2013, vol. 14, pp. 7–23. DOI: 10.1038/nrn3379
23. Pascoe M.C., Parker A.G. Physical Activity and Exercise as a Universal Depression Prevention in Young People: A Narrative Review. Early Intervention in Psychiatry, 2019, vol. 13, pp. 733–739. DOI: 10.1111/eip.12737
24. Santos-Lozano A., Pareja-Galeano H., Sanchis-Gomar F. et al. Physical Activity and Alzheimer Disease: A Protective Association. Mayo Clinic Proceedings, 2016, vol. 91, pp. 999–1020. DOI: 10.1016/j.mayocp.2016.04.024
25. Maak S., Norheim F., Drevon C.A. et al. Progress and Challenges in the Biology of FNDC5 and Irisin. Endocrine Reviews, 2021, vol. 42, pp. 436–456. DOI: 10.1210/endrev/bnab003
26. Lu Y., Bu F.-Q., Wang F. et al. Recent Advances on the Molecular Mechanisms of Exercise‑Induced Improvements of Cognitive Dysfunction. Translational Neurodegeneration, 2023, vol. 12, art. 9. DOI: 10.1186/s40035-023-00341-5
27. Schulkin J. Evolutionary Basis of Human Running and its Impact on Neural Function. Frontiers in Systems Neuroscience, 2016, vol. 10, art. 59. DOI: 10.3389/fnsys.2016.00059
28. Tahara Y., Aoyama S., Shibata S. The Mammalian Circadian Clock and its Entrainment by Stress and Exercise. Journal of Physiological Sciences, 2017, vol. 67, pp. 531–534. DOI: 10.1007/ s12576-016-0450-7
29. Burtscher J., Millet G.P., Place N. et al. The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection. International Journal of Molecular Sciences, 2021, vol. 22, art. 6479. DOI: 10.3390/ijms22126479
30. Li D.J., Li Y.H., Yuan H.B. et al. The Novel Exercise-Induced Hormone Irisin Protects Against Neuronal Injury via Activation of the Akt and ERK1/2 Signaling Pathways and Contributes to the Neuroprotection of Physical Exercise in Cerebral Ischemia. Metabolism, 2017, vol. 68, pp. 31–42. DOI: 10.1016/j.metabol.2016.12.003
31. Schroeder A.M., Truong D., Loh D.H. et al. Voluntary Scheduled Exercise Alters Diurnal Rhythms of Behaviour, Physiology and Gene Expression in Wild-Type and Vasoactive Intestinal Peptide-Deficient Mice. Journal of Physiology, 2012, vol. 590, pp. 6213–6226. DOI: 10.1113/jphysiol.2012.233676
32. Weinert D., Schottner K. An Inbred Lineage of Djungarian Hamsters with a Strongly Attenuated Ability to Synchronize. Chronobiology Interbational, 2007, vol. 24, pp. 1065–1079. DOI: 10.1080/07420520701791588
33. Wrann C.D. FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain. Brain Plasticity, 2015, vol. 1, pp. 55–61. DOI: 10.3233/BPL-150019
34. Wu J., Spiegelman B.M. Irisin ERKs the Fat. Diabetes, 2014, vol. 63, pp. 381–383. DOI: 10.2337/db13-1586
35. Zhang J., Zhang W. Can Irisin Be a Linker Between Physical Activity and Brain Function? BioMolecular Concepts, 2016, vol. 7, pp. 253–258. DOI: 10.1515/bmc-2016-0012
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7. Oguri Y., Shinoda K., Kim H. et al. CD81 Controls Beige Fat Progenitor Cell Growth and Energy Balance via FAK Signaling. Cell, 2020, vol. 182, pp. 563–577. DOI: 10.1016/j.cell.2020.06.021
8. Bilu C., Frolinger-Ashkenazi T., Einat H. et al. Effects of Photoperiod and Diet on BDNF Daily Rhythms in Diurnal Sand Rats. Behavioural Brain Research, 2022, vol. 418, art. 113666. DOI: 10.1016/j.bbr.2021.113666
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10. Lourenco M.V., Frozza R.L., de Freitas G.B. et al. Exercise-Linked FNDC5/Irisin Rescues Synaptic Plasticity and Memory Defects in Alzheimer’s Models. Nature Medicine, 2019, vol. 25, pp. 165–175. DOI: 10.1038/s41591-018-0275-4
11. Waseem R., Shamsi A., Mohammad T. et al. FNDC5/Irisin: Physiology and Pathophysiology. Molecules, 2022, vol. 27, art. 1118. DOI: 10.3390/molecules27031118
12. Hastings M.H., Brancaccio M., Maywood E.S. Circadian Pacemaking in Cells and Circuits of the Suprachiasmatic Nucleus. Journal of Neuroendocrinology, 2014, vol. 26, pp. 2–10. DOI: 10.1111/jne.12125
13. Hastings M.H., Maywood E.S., Brancaccio M. Generation of Circadian Rhythms in the Suprachiasmatic Nucleus. Nature Reviews Neuroscience, 2018, vol. 19, pp. 453–469. DOI: 10.1038/s41583-018-0026-z
14. Zhang W., Chang L., Zhang C. et al. Irisin: a Myokine with Locomotor Activity. Neuroscience Letters, 2015, vol. 595, pp. 7–11. DOI: 10.1016/j.neulet.2015.03.069
15. Estell E.G., Le P.T., Vegting Y. et al. Irisin Directly Stimulates Osteoclastogenesis and Bone Resorption In Vitro and In Vivo. eLife, 2020, vol. 9, art. e58172. DOI: 10.7554/eLife.58172
16. Qiao X., Nie Y., Ma Y. et al. Irisin Promotes Osteoblast Proliferation and Differentiation via Activating the MAP Kinase Signaling Pathways. Scientific Reports, 2016, vol. 6, art. 18732. DOI: 10.1038/srep18732
17. Bi J., Zhang J., Ren Y. et al. Irisin Reverses Intestinal Epithelial Barrier Dysfunction During Intestinal Injury via Binding to the Integrin αVβ5 Receptor. Journal of Cellular and Molecular Medicine, 2020, vol. 24, pp. 996–1009. DOI: 10.1111/jcmm.14811
18. Zhang Y., Li R., Meng Y. et al. Irisin Stimulates Browning of White Adipocytes Through Mitogen-Activated Protein Kinase p38 MAP Kinase and ERK MAP Kinase Signaling. Diabetes, 2014, vol. 63, pp. 514–525. DOI: 10.2337/db13-1106
19. Jodeiri Farshbaf M., Alvina K. Multiple Roles in Neuroprotection for the Exercise Derived Myokine Irisin. Frontiers in Aging Neuroscience, 2021, vol. 13, art. 649929. DOI: 10.3389/fnagi.2021.649929
20. Mendoza G., Merchant H. Motor System Evolution and the Emergence of High Cognitive Functions. Progress in Neurobiology, 2014, vol. 122, pp. 73–93. DOI: 10.1016/j.pneurobio.2014.09.001
21. Rabiee F., Lachinani L., Ghaedi S. et al. New Insights into the Cellular Activities of Fndc5/Irisin and its Signaling Pathways. Cell & Bioscience, 2020, vol. 10, art. 51. DOI: 10.1186/s13578-020-00413-3
22. Park H., Poo M.M. Neuroprophin Regulation of Neural Circuit Development and Function. Nature Review Neurocsience, 2013, vol. 14, pp. 7–23. DOI: 10.1038/nrn3379
23. Pascoe M.C., Parker A.G. Physical Activity and Exercise as a Universal Depression Prevention in Young People: A Narrative Review. Early Intervention in Psychiatry, 2019, vol. 13, pp. 733–739. DOI: 10.1111/eip.12737
24. Santos-Lozano A., Pareja-Galeano H., Sanchis-Gomar F. et al. Physical Activity and Alzheimer Disease: A Protective Association. Mayo Clinic Proceedings, 2016, vol. 91, pp. 999–1020. DOI: 10.1016/j.mayocp.2016.04.024
25. Maak S., Norheim F., Drevon C.A. et al. Progress and Challenges in the Biology of FNDC5 and Irisin. Endocrine Reviews, 2021, vol. 42, pp. 436–456. DOI: 10.1210/endrev/bnab003
26. Lu Y., Bu F.-Q., Wang F. et al. Recent Advances on the Molecular Mechanisms of Exercise‑Induced Improvements of Cognitive Dysfunction. Translational Neurodegeneration, 2023, vol. 12, art. 9. DOI: 10.1186/s40035-023-00341-5
27. Schulkin J. Evolutionary Basis of Human Running and its Impact on Neural Function. Frontiers in Systems Neuroscience, 2016, vol. 10, art. 59. DOI: 10.3389/fnsys.2016.00059
28. Tahara Y., Aoyama S., Shibata S. The Mammalian Circadian Clock and its Entrainment by Stress and Exercise. Journal of Physiological Sciences, 2017, vol. 67, pp. 531–534. DOI: 10.1007/ s12576-016-0450-7
29. Burtscher J., Millet G.P., Place N. et al. The Muscle-Brain Axis and Neurodegenerative Diseases: The Key Role of Mitochondria in Exercise-Induced Neuroprotection. International Journal of Molecular Sciences, 2021, vol. 22, art. 6479. DOI: 10.3390/ijms22126479
30. Li D.J., Li Y.H., Yuan H.B. et al. The Novel Exercise-Induced Hormone Irisin Protects Against Neuronal Injury via Activation of the Akt and ERK1/2 Signaling Pathways and Contributes to the Neuroprotection of Physical Exercise in Cerebral Ischemia. Metabolism, 2017, vol. 68, pp. 31–42. DOI: 10.1016/j.metabol.2016.12.003
31. Schroeder A.M., Truong D., Loh D.H. et al. Voluntary Scheduled Exercise Alters Diurnal Rhythms of Behaviour, Physiology and Gene Expression in Wild-Type and Vasoactive Intestinal Peptide-Deficient Mice. Journal of Physiology, 2012, vol. 590, pp. 6213–6226. DOI: 10.1113/jphysiol.2012.233676
32. Weinert D., Schottner K. An Inbred Lineage of Djungarian Hamsters with a Strongly Attenuated Ability to Synchronize. Chronobiology Interbational, 2007, vol. 24, pp. 1065–1079. DOI: 10.1080/07420520701791588
33. Wrann C.D. FNDC5/Irisin – Their Role in the Nervous System and as a Mediator for Beneficial Effects of Exercise on the Brain. Brain Plasticity, 2015, vol. 1, pp. 55–61. DOI: 10.3233/BPL-150019
34. Wu J., Spiegelman B.M. Irisin ERKs the Fat. Diabetes, 2014, vol. 63, pp. 381–383. DOI: 10.2337/db13-1586
35. Zhang J., Zhang W. Can Irisin Be a Linker Between Physical Activity and Brain Function? BioMolecular Concepts, 2016, vol. 7, pp. 253–258. DOI: 10.1515/bmc-2016-0012
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