Зимняя спячка млекопитающих как стратегия адаптации к неблагоприятным факторам среды

Цель: проанализировать имеющиеся литературные данные о путях выживания гетеротермных эндотермов в неблагоприятных экологических условиях, в периоды низкой доступности пищевых ресурсов.
В статье приводятся данные о различиях суточной и сезонной гетеротермии. Выделены особенности подготовки к зимней спячке факультативных и облигатных гибернаторов. Рассмотрены гипотезы происхождения и эволюции гетеротермии. Обобщены наиболее вероятные причины периодических пробуждений животных от спячки в период гибернации. Значительное внимание уделено перестройке энергетического обмена в период зимней спячки – переходу от углеводного к липидному метаболизму. Проанализированы данные, свидетельствующие о значении жирных кислот, получаемых с пищей в активный летний период, как для синтеза запасных жиров, так и в регуляции самой спячки. Опираясь на данные о накоплении в тканях моноеновых жирных кислот в период спячки, высказано предположение об их адаптивном значении, направленном на ограничение окислительного стресса и сохранение жизненно важных функций клеток.
Приведённые данные могут быть использованы как для проведения фундаментальных исследований адаптивных механизмов взаимодействия организма со средой, так и для решения практических задач, особенно при выборе моделей ограничения калорий или прерывистого голодания, а также изучения толерантности тканей к окислительному стрессу и устойчивости к повреждающему действию ишемии‐реперфузии.

1. Kronfeld-Schor N., Dayan T. Thermal ecology, environments, communities, and global change: energy intake and expenditure in endotherms // Annual Review of Ecology, Evolution, and Systematics. 2013. V. 44. P. 461–480. https://doi.org/10.1146/annurev-ecolsys-110512-135917

2. Humphries M.M., Thomas D.W., Kramer D.L. The role of energy availability in mammalian hibernation: a costbenefit approach // Physiological and Biochemical Zoology. 2003. V. 76. N 2. P. 165–179.

3. Geiser F. Hibernation // Current Biology. 2013. V. 23. N 5. P. 188–193. DOI: 10.1016/j.cub.2013.01.062

4. Heldmaier G., Ortmann S., Elvert R. Natural hypometabolism during hibernation and daily torpor in mammals // Respiratory Physiology and Neurobiology. 2004. V. 141. N 3. P. 17–29. https://doi.org/10.1016/j.resp.2004.03.014

5. Geiser F. Seasonal expression of avian and mammalian daily torpor and hibernation: not a simple summer-winter affair // Frontiers in Physiology. 2020. V. 11. https://doi.org/10.3389/fphys.2020.00436

6. Ruf T., Geiser F. Daily torpor and hibernation in birds and mammals // Biological Reviews Cambridge Philosophycal Society. 2015. V. 90. N 3. P. 891–926. https://doi.org/10.1111/brv.12137

7. Carey H.V., Andrews M.T., Martin S.L. Mammalian hibernation: cellular and molecular responses to depressed metabolism and low temperature // Physiological Reviews. 2003. V. 83. N 4. P. 1153–1181. https://doi.org/10.1152/physrev.00008.2003

8. Liu J.N., Karasov W.H. Metabolism during winter in a subtropical hibernating bat, the Formosan leaf-nosed bat (Hipposideros terasensis) // Journal of Mammalogy. 2012. V. 93. N 1. P. 220–228. https://doi.org/10.1644/11-MAMM-A-144.1

9. Nowack J., Levesque D.L., Reher S., Dausmann K.H. Variable climates lead to varying phenotypes: «weird» mammalian torpor and lessons from non-holarctic species // Frontiers in Ecology and Evolution. 2020. V. 8. https://doi.org/10.3389/fevo.2020.00060

10. Geiser F. Yearlong hibernation in a marsupial mammal // The Science of Nature. 2007. V. 94. P. 941–944. http://dx.doi.org/10.1007/s00114-007-0274-7

11. Toien O., Blake J., Barnes B.M. Thermoregulation and energetics in hibernating black bears: Metabolic rate and the mystery of multi-day body temperature cycles // Journal of Comparative Physiology. 2015. V. 185. N 4. P. 447–461. http://dx.doi.org/10.1007/s00360-015-0891-y

12. Giroud S., Habold C., Nespolo R.F., Mejías C., Terrien J., Logan S.M., Henning R.H., Storey K.B. The torpid state: recent advances in metabolic adaptations and protective mechanisms // Frontiers Physiology. 2021. V. 11. Article id: 623665. https://doi.org/10.3389%2Ffphys.2020.623665

13. Ануфриев А.И. Очерки экологии и зимней спячки млекопитающих в условиях холода. Новосибирск: СО РАН, 2023. 152 с.

14. Mohr S.M., Bagriantsev S.N., Gracheva E.O. Molecular and physiological adaptations of hibernation: the solution to environmental challenges // Annual Review of Cell and Development Biology. 2020. V. 36. P. 315–338. https://doi.org/10.1146/annurev-cellbio-012820-095945

15. Chayama Y., Ando L., Tamura Y., Miura M., Yamaguchi Y. Decreases in body temperature and body mass constitute pre-hibernation remodelling in the Syrian golden hamster, a facultative mammalian hibernator // Royal Society Open Science. 2016. V. 3. N 4. https://doi.org/10.1098/rsos.160002

16. Florant G., Healy J. The regulation of food intake in mammalian hibernators: a review // Journal of omparative Physiology B. 2012. V. 182. N 4. P. 451–67. https://doi.org/10.1007/s00360-011-0630-y

17. Geiser F. Ontogeny and phylogeny of endothermy and torpor in mammals and birds // Comparative Biochemistry and Physiology Part A: Molecular and Integrative Physiology. 2008. V. 150. N 2. P. 176–80. https://doi.org/10.1016/j.cbpa.2007.02.041

18. Harris M.B., Olson L.E., Milsom W.K. The origin of mammalian heterothermy: a case for perpetual youth? // Life in the Cold: Evolution, Mechanisms, Adaptation, and Application. Twelfth International Hibernation Symposium. 2004. P. 144–52.

19. Grigg G.C., Beard L.A., Augee M.L. The evolution of endothermy and its diversity in mammals and birds // Physiological and Biochemical Zoology. 2004. V. 77. N 6. P. 982–997. https://doi.org/10.1086/425188

20. Lovegrove B.G., Ruf T., Bieber C., Arnold W., Millesi E., eds. A single origin of heterothermy in mammals. Living in a Seasonal World: Thermoregulatory and Metabolic Adaptations. Berlin: Springer, 2012. P. 3–11.

21. Andrews M.T. Molecular interactions underpinning the phenotype of hibernation in mammals // The Journal of Experimental Biology. 2019. V. 222. Iss. 2. Article Id: jeb160606. https://doi.org/10.1242/jeb.160606

22. Klug B.J., Brigham R.M. Changes to Metabolism and Cell Physiology that Enable Mammalian Hibernation // Springer Science Reviews. 2015. V. 3. N 1. P. 39–56. http://dx.doi.org/10.1007/s40362-015-0030-x

23. Frare C., Williams C.T., Drew K.L. Thermoregulation in hibernating mammals: The role of the «thyroid hormones system» // Molecular and Cellular Endocrinology. 2021. Article id: 111054. https://doi.org/10.1016/j.mce.2020.111054

24. Staples J.F. Metabolic flexibility: hibernation, torpor, and estivation // Comprehensive Physiology. 2016. V. 6. N 2. P. 737–771. https://doi.org/10.1002/cphy.c140064

25. Klichkhanov N.K., Nikitina E.R., Shihamirova Z.M., Astaeva M.D., Chalabov S.I., Krivchenko A.I. Erythrocytes of little ground squirrels undergo reversible oxidative stress during arousal from hibernation // Frontiers Physiology. 2021. V. 12. https://doi.org/10.3389/fphys.2021.730657

26. Buck C.L., Barnes B.M. Effects of ambient temperature on metabolic rate, respiratory quotient, and torpor in an arctic hibernato // American Journal Physiology-Regulatory, Integrative and Comparative Physiology. 2000. V. 279. N 1. P. 255–262. https://doi.org/10.1152/ajpregu.2000.279.1.r255

27. Geiser F. Hibernation: Endotherms // Encyclopedia of life sciences. 2001. http://dx.doi.org/10.1038/npg.els.0003215

28. Wang L.C.H., Lee T.F. Torpor and hibernation in mammals: metabolic, physiological, and biochemical adaptations // Comprehensive Physiology. 2011. https://doi.org/10.1002/cphy.cp040122

29. Ануфриев А.И. Температурная регуляция ритмов зимней спячки // Природные ресурсы Арктики и Субарктики. 2020. Т. 25. N 1. С.60–67. DOI 10.31242/2618-9712-2020-25-1-6

30. Milsom W.K., Jackson D.C. Hibernation and gas exchange // Comprehensive Physiology. 2011. V. 1. N 1. P. 397–420. https://doi.org/10.1002/cphy.c090018

31. Maginniss L.A., Milsom W.K. Effects of hibernation on blood oxygen transport in the golden-mantled ground squirrel // Respiration Physiology. 1994. V. 95. N 2. P. 195–208. https://doi.org/10.1016/0034-5687(94)90116-3

32. Karpovich S.A., Tøien O., Buck C.L., Barnes B.M. Energetics of arousal episodes in hibernating arctic ground squirrels // Journal of Comparative Physiology B. 2009. V. 179. N 6. P. 691–700. https://doi.org/10.1007/s00360-009-0350-8

33. Wang L.C. H. Time patterns and metabolic rates of natural torpor in the Richardson's ground squirrel // Canadian Journal of Zoology. 1979. V. 57. P. 149–155. DOI:10.1139/Z79-012

34. Jinka T.R., Rasley B.T., Drew K.L. Inhibition of NMDAtype glutamate receptors induces arousal from torpor in hibernating arctic ground squirrels (Urocitellus parryii) // Journal of Neurochemistry. 2012. V. 122. P. 934–940. https://doi.org/10.1111/j.1471-4159.2012.07832.x

35. Zimmerman M.L. Carbohydrate and torpor duration in hibernating golden-mantled ground squirrels (Citellus lateralis) // Journal of Comparative Physiology. 1982. V. 147. N 1. P. 129–135. URL: http://hdl.handle.net/2027.42/47127

36. Ruf T., Gasch K., Stalder G., Gerritsmann H., Giroud S. An hourglass mechanism controls torpor bout length in hibernating garden dormice // Journal of Experimental Biology. 2021. V. 224. N 23. Article Id: jeb243456. https://doi.org/10.1242%2Fjeb.243456

37. Prendergast B.J, Freeman D.A, Zucker I, Nelson R.J. Periodic arousal from hibernation is necessary for initiation of immune responses in ground squirrels // American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2002. V. 282. N 4. P. 1054–1062. https://doi.org/10.1152/ajpregu.00562.2001

38. Bouma H.R., Koese F.G.M., Kok J.W., Talaei F., Boerema A.S., Herwig A., Draghiciu O., van Buiten A., Epema A.H., van Dam A., Strijkstra A.M., Henning R.H. Low body temperature governs the decline of circulating lymphocytes during hibernation through sphingosine-1-phosphate // Proceedings of the National Academy of Sciences (PNAS). 2011. V. 108. N 5. P. 2052–2057. https://doi.org/10.1073/pnas.1008823108

39. Ruediger J., van der Zee E.A., Strijkstra A.M., Aschoff A., Daan S., Hut R.A. Dynamics in the ultrastructure of asymmetric axospinous synapses in the frontal cortex of hibernating European ground squirrels (Spermophilus citellus) // Synapse. 2007. V. 61. N 5. P. 343–352. https://doi.org/10.1002/syn.20380

40. Popov V.I., Bocharova L.S., Bragin A.G. Repeated changes of dendritic morphology in the hippocampus of ground squirrels in the course of hibernation // Neuroscience. 1992. V. 48. N 1. P. 45–51. https://doi.org/10.1016/0306-4522(92)90336-z

41. Arendt T., Bullmann T. Neuronal plasticity in hibernation and the proposed role of the microtubuleassociated protein tau as a “master switch” regulating synaptic gain in neural networks // American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2013. V. 305. N 5. P. R478–489. https://doi.org/10.1152/ajpregu.00117.2013

42. Dark J. Annual lipid cycles in hibernators: integration of physiology and behavior // Annual Review of Nutrition. 2005. V. 25. P. 469–497. https://doi.org/10.1146/annurev.nutr.25.050304.092514

43. Storey K.B. Out cold: biochemical regulation of mammalian hibernation – a mini-review // Gerontology. 2010. V. 56. N 2. P. 220–230. https://doi.org/10.1159/000228829

44. Buck M.J., Squire T.L., Andrews M.T. Coordinate expression of the PDK4 gene: a means of regulating fuel selection in a hibernating mammal // Physiological Genomics. 2002. V. 8. N 1. P. 5–13. https://doi.org/10.1152/physiolgenomics.00076.2001

45. Healy G.N., Clark B.K., Winkler E.A., Gardiner P.A., Brown W.J., Matthews C.E. Measurement of adults sedentary time in population-based studies // American Journal of Preventive Medicine. 2011. V. 41. N 2. P. 216–27. https://doi.org/10.1016/j.amepre.2011.05.005

46. Puchalska P., Crawford P.A. Multi-dimensional roles of ketone bodies in fuel metabolism, signaling, and therapeutics // Cell Metabolism. 2017. V. 25. N 2. P. 262–284. https://doi.org/10.1016%2Fj.cmet.2016.12.022

47. García-Rodríguez D., Giménez-Cassina A. Ketone bodies in the brain beyond fuel metabolism: from excitability to gene expression and cell signaling // Frontiers in Molecular Neuroscience. 2021. V. 14. https://doi.org/10.3389/fnmol.2021.732120

48. Andrews M.T., Russeth K.P., Drewes L.R., Henry P.G. Adaptive mechanisms regulate preferred utilization of ketones in the heart and brain of a hibernating mammal during arousal from torpor // The American Journal of Physiology-Regulatory, Integrative and Comparative Physiology. 2009. V. 296. N 2. P. 383–393. https://doi.org/10.1152%2Fajpregu.90795.2008

49. Aloia R.C. Lipid, fluidity, and functional studies of the membranes of hibernating mammals. In: Aloia R.C., Curtain C.C., Gordon L.M. (eds.), Advances in membrane fluidity. Alan R. Liss, Inc., New York. 1988. P. 1–39.

50. Giroud S., Frare C., Strijkstra A., Boerema A., Arnold W., Ruf T. Membrane phospholipid fatty acid composition regulates cardiac SERCA activity in a hibernator, the Syrian hamster (Mesocricetus auratus) // PLoS ONE. 2013. V. 8. N 5. Article Id: e63111. https://doi.org/10.1371%2Fjournal.pone.0063111

51. Ruf T., Arnold W. Effects of polyunsaturated fatty acids on hibernation and torpor: a review and hypothesis // American Journal of Physiology. Regulatory, Integrative and Comparative Physiology. 2008. V. 294. N 3. P. 1044–1052. https://doi.org/10.1152/ajpregu.00688.2007

52. Arnold W., Ruf T., Frey-Roos F., Bruns U. Diet-Independent remodeling of cellular membranes precedes seasonally changing body temperature in a hibernator // PLoS ONE. 2011. V. 6. https://doi.org/10.1371/journal.pone.0018641

53. Hill V.L., Florant G.L. The effect of a linseed oil diet on hibernation in yellow-bellied marmots (Marmota flaviventris) // Physiology and Behavior. 2000. V. 68. N 4. P. 431–437. https://doi.org/10.1016/s0031-9384(99)00177-8

54. Giroud S., Stalder G., Gerritsmann H., Kübber-Heiss A., Kwak J., Arnold W., Ruf T. Dietary lipids affect the onset of hibernation in the garden dormouse (Eliomys quercinus): implications for cardiac function // Frontiers Physiology. 2018. V. 18. https://doi.org/10.3389/fphys.2018.01235

55. Frank C.L. Short-term variations in diet fatty acid composition and torpor by ground squirrels // Journal of Mammalogy. 2002. V. 83. N 4. P. 1013–1019. https://doi.org/10.1644/15451542(2002)083%3C1013:STVIDF%3E2.0.CO;2

56. Frank C.L., Hood W.R., Donnelly M.C. The role of alphalinolenic acid (18:3) in mammalian torpor. In: Barnes B.M., Carey H.V., eds. Life in the cold: evolution, mechanisms, adaptation, and application. AK: University of Alaska Fairbanks, 2004. pp. 71–80.

57. Rice S.A., Mikes M., Bibus D., Berdyshev E., Reisz J.A., Gehrke S., Bronova I., D'Alessandro A., Drew K.L. Omega 3 fatty acids stimulate thermogenesis during torpor in the Arctic Ground Squirrel // Scientific Reports. 2021. V. 11. N 1340. https://doi.org/10.1038/s41598-020-78763-8

58. Arnold W., Giroud S., Valencak T.G, Ruf T. Ecophysiology of omega fatty acids: a lid for every jar // Physiology (Bethesda). 2015. V. 30. N 3. P. 232–240. DOI: 10.1152/physiol.00047.2014

59. Watkins S.M., Carter L.C., German J.B. Docosahexaenoic acid accumulates in cardiolipin and enhances HT-29 cell oxidant production // Journal of Lipid Research. 1998. V. 39. N 8. P. 1583–1588.

60. Vuarin P., Henry P.Y., Guesnet P., Alessandri J.M., Aujard F., Perret M., Pifferi F. Shallow hypothermia depends on the level of fatty acid unsaturation in adipose and liver tissues in a tropical heterothermic primate // Journal of Thermal Biology. 2014. V. 43. P. 81–88. https://doi.org/10.1016/j.jtherbio.2014.05.002

61. Vuarin P, Henry P.Y, Perret M, Pifferi F. Dietary Supplementation with n-3 Polyunsaturated Fatty Acids Reduces Torpor Use in a Tropical Daily Heterotherm // Physiological and Biochemical Zoology. 2016. V. 89. N 6. P. 536–545. https://doi.org/10.1086/688659

62. Munro D., Thomas D.W. The role of polyunsaturated fatty acids in the expression of torpor by mammals: a review // Zoology (Jena). 2004. V. 107. N 1. P. 29–48. https://doi.org/10.1016/j.zool.2003.12.001

63. Price E.R., Armstrong C., Guglielmo C.G., Staples J.F. Selective mobilization of saturated fatty acids in isolated adipocytes of hibernating 13-lined ground squirrels Ictidomys tridecemlineatus // Physiological and Biochemical Zoology. 2013. V. 86. N 2. P. 205–212. https://doi.org/10.1086/668892

64. Giroud S., Chery I., Bertile F., Bertrand-Michel J., Tascher G., Gauquelin-Koch G., Arnemo J.M., Swenson J.E., Singh N.J., Lefai E., Evans A.L., Simon C., Blanc S. Lipidomics reveals seasonal shifts in a large-bodied hibernator, the brown bear // Frontiers in Physiology. 2019. V. 10. https://doi.org/10.3389%2Ffphys.2019.00389

65. Kulagina T.P., Popova S.S., Aripovsky A.V. Seasonal changes in the content of fatty acids in the myocardium and m. longissimus dorsi of the Long-Tailed Ground Squirrel Urocitellus undulates // Biophysics. 2021. V. 66. N 6. P. 1004–1010. DOI: 10.1134/S0006350921060087

66. Kodali S.T., Kauffman P., Kotha S.R., Yenigalla A., Veeraraghavan R., Pannu S.R., Hund T.J., Satoskar A.R., McDaniel J.C., Maddipati R.K., Parinandi N.L. Oxidative lipidomics: analysis of oxidized lipids and lipid peroxidation in biological systems with relevance to health and disease. In: Berliner L., Parinandi N., eds. Measuring Oxidants and Oxidative Stress in Biological Systems. Biological Magnetic Resonance. 2020. V. 34. https://doi.org/10.1007/978-3-030-47318-1_5