Pathophysiological Role of Thermoregulatory Reactions in the Development of Common Cold Diseases: Paradigmatic Shift from Pathogen-Centric to Host-Response Model: A Critical Review
DOI:
https://doi.org/10.12775/PPS.2025.24.64946Keywords
thermoregulation, cold diseases, immune response, adaptation, pathogenesis, host-responsive modelAbstract
This review synthesizes research on the pathophysiological role of thermoregulatory responses in the development of cold-related diseases, focusing on the physiological mechanisms underlying thermoregulation and their interaction with the immune system. Special attention is given to the effects of cold stress on mucosal barriers and systemic effects, the role of gut microbiota in thermoregulation considering age and gender differences, as well as the application of host-responsive models in clinical settings with potential therapeutic approaches.
The aim of the review was to evaluate thermoregulatory-immune interactions, analyze the impact of cold stress on mucosal integrity and systemic inflammation, compare age and gender variations in gut microbiota, and identify therapeutic strategies targeting microbiota and immune modulation.
A critical analysis of multidisciplinary studies using animal and human models with molecular, immunological, and microbiome profiling was conducted. Results indicate that cold exposure modulates immune cell populations and cytokine profiles, disrupts gut barrier function through changes in tight junctions and inflammatory pathways, and consistently alters gut microbiota diversity with limited research on sex and age effects.
Integration of these findings highlights the complex interaction between thermoregulation, immunity, and microbiota in cold-related diseases. These concepts inform the development of targeted clinical interventions and emphasize the need for standardized integrative models.
References
Arora, T., & Bäckhed, F. (2016). The gut microbiota and metabolic disease: Current understanding and future perspectives. Journal of Internal Medicine, 280(4), 339-349. https://doi.org/10.1111/joim.12508
Bae, J. Y., Woo, J., Kang, S., & Shin, K. O. (2018). Effects of detraining and retraining on muscle energy-sensing network and meteorin-like levels in obese mice. Lipids in Health and Disease, 17(1), 90. https://doi.org/10.1186/s12944-018-0751-3
Becker, M., Serr, I., Salb, V. K., Ott, V. B., Mengel, L. A., Blüher, M., Weigmann, B., Hauner, H., Tschöp, M. H., & Daniel, C. (2019). Short-term cold exposure supports human Treg induction in vivo. Molecular Metabolism, 28, 73-82. https://doi.org/10.1016/j.molmet.2019.08.002
Blondin, D. P., & Haman, F. (2018). Shivering and nonshivering thermogenesis in skeletal muscles. Handbook of Clinical Neurology, 156, 153-173. https://doi.org/10.1016/B978-0-444-63912-7.00010-2
Bo, T., Tang, L., Xu, X., Liu, M., Wen, J., Lv, J., & Wang, D. (2023). Role of gut microbiota in the postnatal thermoregulation of Brandt's voles. Cell Reports, 42(9), 113021. https://doi.org/10.1016/j.celrep.2023.113021
Bo, T., Zhang, X., Wen, J., Deng, K., Qin, X., & Wang, D. (2019). The microbiota-gut-brain interaction in regulating host metabolic adaptation to cold in male Brandt's voles (Lasiopodomys brandtii). The ISME Journal, 13(12), 3037-3053. https://doi.org/10.1038/s41396-019-0492-y
Bongers, K. S., Chanderraj, R., Woods, R. J., McDonald, R. A., Adame, M. D., Falkowski, N. R., Brown, C. A., Baker, J. L., Winner, K., Fergle, D., Hinkle, K. J., Standke, A., Vendrov, K. C., Young, V. B., Stringer, K. A., Sjoding, M. W., & Dickson, R. P. (2022). The gut microbiome modulates body temperature both in sepsis and health. American Journal of Respiratory and Critical Care Medicine, 206(6), 754-764. https://doi.org/10.1164/rccm.202201-0161OC
Brychta, R. J., & Chen, K. Y. (2017). Cold-induced thermogenesis in humans. European Journal of Clinical Nutrition, 71(3), 345-352. https://doi.org/10.1038/ejcn.2016.223
Buijs, R. M., la Fleur, S. E., Wortel, J., Van Heyningen, C., Zuiddam, L., Mettenleiter, T. C., Kalsbeek, A., Nagai, K., & Niijima, A. (2003). The suprachiasmatic nucleus balances sympathetic and parasympathetic output to peripheral organs through separate preautonomic neurons. Journal of Comparative Neurology, 464(1), 36-48. https://doi.org/10.1002/cne.10765
Cannon, B., & Nedergaard, J. (2004). Brown adipose tissue: Function and physiological significance. Physiological Reviews, 84(1), 277-359. https://doi.org/10.1152/physrev.00015.2003
Castellani, J. W., & Tipton, M. J. (2015). Cold stress effects on exposure tolerance and exercise performance. Comprehensive Physiology, 6(1), 443-469. https://doi.org/10.1002/cphy.c140081
Chang, J. C., Durinck, S., Chen, M. Z., Martinez-Martin, N., Zhang, J. A., Lehoux, I., Li, H., Lin, M., Wu, J., Bainbridge, T. W., Ernst, J. A., Ramani, S. R., Paduchuri, S., Kates, L., Solon, M., Buechler, M. B., Castiglioni, A., Thai, M., Breart, B., & Sonoda, J. (2019). Adaptive adipose tissue stromal plasticity in response to cold stress and antibody-based metabolic therapy. Scientific Reports, 9(1), 8346. https://doi.org/10.1038/s41598-019-45354-1
Chang, Y., Zhang, Z., Cai, J., Wang, C., Liu, D., Liu, Z., & Xu, C. (2024). Coevolution of specific gut microbiota of Min pig with host cold adaptation through enhanced vitamin B1 synthesis. Frontiers in Microbiology, 15, 1448090. https://doi.org/10.3389/fmicb.2024.1448090
Chen, K. Y., Brychta, R. J., Linderman, J. D., Smith, S., Courville, A., Dieckmann, W., Herscovitch, P., Millo, C. M., Remaley, A., Lee, P., & Celi, F. S. (2013). Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. Journal of Clinical Endocrinology & Metabolism, 98(7), E1218-E1223. https://doi.org/10.1210/jc.2012-4213
Chevalier, C., Stojanović, O., Colin, D. J., Suarez-Zamorano, N., Tarallo, V., Veyrat-Durebex, C., Rigo, D., Fabbiano, S., Stevanović, A., Hagemann, S., Montet, X., Seimbille, Y., Zamboni, N., Hapfelmeier, S., & Trajkovski, M. (2015). Gut microbiota orchestrates energy homeostasis during cold. Cell, 163(6), 1360-1374. https://doi.org/10.1016/j.cell.2015.11.004
Cypess, A. M., Lehman, S., Williams, G., Tal, I., Rodman, D., Goldfine, A. B., Kuo, F. C., Palmer, E. L., Tseng, Y. H., Doria, A., Kolodny, G. M., & Kahn, C. R. (2009). Identification and importance of brown adipose tissue in adult humans. New England Journal of Medicine, 360(15), 1509-1517. https://doi.org/10.1056/NEJMoa0810780
Daanen, H. A., & Van Marken Lichtenbelt, W. D. (2016). Human whole body cold adaptation. Temperature, 3(1), 104-118. https://doi.org/10.1080/23328940.2015.1135688
Di, Y., Li, H., Yang, J., Feng, M., Wang, S., Li, W., Wang, X., Zhu, Y., Shi, Y., Feng, R., & Qü, B. (2024). PPARγ/NF-κB axis contributes to cold-induced resolution of experimental colitis and preservation of intestinal barrier. Biochimica et Biophysica Acta - Molecular Basis of Disease, 1870(6), 167326. https://doi.org/10.1016/j.bbadis.2024.167326
Eccles, R. (2002). An explanation for the seasonality of acute upper respiratory tract viral infections. Acta Oto-Laryngologica, 122(2), 183-191. https://doi.org/10.1080/00016480252814207
Fendrick, A. M., Monto, A. S., Nightengale, B., & Sarnes, M. (2003). The economic burden of non-influenza-related viral respiratory tract infection in the United States. Archives of Internal Medicine, 163(4), 487-494. https://doi.org/10.1001/archinte.163.4.487
Fromme, T., & Klingenspor, M. (2011). Uncoupling protein 1 expression and high-fat diets. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 300(1), R1-R8. https://doi.org/10.1152/ajpregu.00411.2010
Ganeshan, K., Nikkanen, J., Man, K., Leong, Y. A., Sogawa, Y., Maschek, J. A., Van Ry, T., Chagwedera, D. N., Cox, J. E., & Chawla, A. (2019). Energetic trade-offs and hypometabolic states promote disease tolerance. Cell, 177(2), 399-413.e12. https://doi.org/10.1016/j.cell.2019.01.050
Giunta, S., Wei, Y., Xu, K., & Xia, S. (2022). Cold‐inflammaging: When a state of homeostatic‐imbalance associated with aging precedes the low‐grade pro‐inflammatory‐state (inflammaging): Meaning, evolution, inflammaging phenotypes. Clinical and Experimental Pharmacology and Physiology, 49(9), 925-934. https://doi.org/10.1111/1440-1681.13686
Gmoshinski, I. V., & Nikityuk, D. B. (2023). Arctic stress: Mechanisms and experimental models. Vestnik Rossiĭskoĭ Akademii Meditsinskikh Nauk, 77(6), 447-457. https://doi.org/10.15690/vramn2209
Gozhenko, A. I. (1979). Adaptatsionno-kompensatornye izmeneniya energeticheskogo obmena i pochechnykh protsessov pri nefrite Mazugi [Adaptive-compensatory changes in energy metabolism and renal processes in Mazugi nephritis]. In Referativnye doklady XIII s"ezda Vsesoyuznogo fiziologicheskogo obshchestva im. I.I. Pavlova [Abstract reports of XIII congress of All-Union physiological society named after I.I. Pavlov] Vol. 1, pp. 32-33. Alma-Ata.
Gozhenko, A. I. (1984). Izmeritel' temperatury [Temperature meter] (USSR Patent No. 1090838).
Gozhenko, A. I. (1984). Ustroystvo dlya izmereniya temperatury [Device for temperature measurement] (USSR Patent No. 1081436).
Gozhenko, A. I. (1985). Meditsinskiy tsifrovoy termometr [Medical digital thermometer] (USSR Patent No. 1173222).
Gozhenko, A. I. (1985). Meditsinskiy tsifrovoy termometr [Medical digital thermometer] (USSR Patent No. 1173223).
Gozhenko, A. I. (1985). Meditsinskiy tsifrovoy termometr [Medical digital thermometer] (USSR Patent No. 1190290).
Gozhenko, A. I. (1987). Diagnostika ostrogo appenditsita s ispol'zovaniem portativnogo teplometra [Diagnosis of acute appendicitis using a portable thermometer]. Klinicheskaya Khirurgiya, 6, 17-19.
Gozhenko, A. I. (2007). Dizregulyatsionnye mekhanizmy sanogeneza [Dysregulatory mechanisms of sanogenesis]. In Sanogenez i zdorov'e cheloveka [Sanogenesis and human health] pp. 108-115. Feniks.
Gozhenko, A. I. (2012). Patogenez: traditsiyni ta suchasni uyavlennya [Pathogenesis: Traditional and modern concepts]. Aktual'ni Problemy Transportnoyi Medytsyny, 1(27), 9-18.
Gozhenko, A. I. (2015). Osnovy postroeniya teorii bolezni: monografiya [Fundamentals of disease theory construction: Monograph]. Feniks.
Gozhenko, A. I. (2015). Programmiruemoe bioupravlenie – teoreticheskaya osnova lechebnykh tekhnologiy budushchego [Programmable biocontrol - theoretical basis of future therapeutic technologies]. In Byulleten' XIV chteniy im. V.V. Podvysotskogo [Bulletin of XIV readings named after V.V. Podvysotsky] pp. 41-42. Odessa.
Gozhenko, A. I. (2015). Sovremennaya teoriya bolezni – teoreticheskaya osnova profilakticheskoy meditsiny [Modern disease theory - theoretical basis of preventive medicine]. Aktual'ni Problemy Transportnoyi Medytsyny, 2(40), 9-17.
Gozhenko, A. I. (2020). Epiteliyal'no-mezenkhimal'naya transformatsiya kletok v patogeneze zabolevaniy COVID-19 [Epithelial-mesenchymal transformation of cells in the pathogenesis of COVID-19 diseases]. Aktual'ni Problemy Transportnoyi Medytsyny, 3(61), 7-18.
Gozhenko, A. I. (2020). Chelovek v evolyutsii biosfery. Pandemiya COVID-19 — vyzov chelovechestvu [Man in the evolution of the biosphere. COVID-19 pandemic - a challenge to humanity]. Aktual'ni Problemy Transportnoyi Medytsyny, 4(62), 7-24.
Hanssen, M. J., Hoeks, J., Brans, B., van der Lans, A. A., Schaart, G., van den Driessche, J. J., Jörgensen, J. A., Boekschoten, M. V., Hesselink, M. K., Havekes, B., Kersten, S., Mottaghy, F. M., van Marken Lichtenbelt, W. D., & Schrauwen, P. (2015). Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nature Medicine, 21(8), 863-865. https://doi.org/10.1038/nm.3891
He, W., Ding, H., Feng, Y., Liu, X., Fang, X., Gao, F., & Shi, B. (2024). Dietary-fat supplementation alleviates cold temperature-induced metabolic dysbiosis and barrier impairment by remodeling gut microbiota. Food & Function, 15(4), 2156-2170. https://doi.org/10.1039/d3fo04916g
Heikkinen, T., & Järvinen, A. (2003). The common cold. The Lancet, 361(9351), 51-59. https://doi.org/10.1016/S0140-6736(03)12162-9
Helman, A., Klochendler, A., Azazmeh, N., Gabai, Y., Horwitz, E., Anzi, S., Swisa, A., Condiotti, R., Granit, R. Z., Nevo, Y., Fixler, Y., Shreibman, D., Zamir, A., Tornovsky-Babeay, S., Dai, C., Glaser, B., Powers, A. C., Shapiro, A. M., Magnuson, M. A., & Ben-Porath, I. (2016). p16Ink4a-induced senescence of pancreatic beta cells enhances insulin secretion. Nature Medicine, 22(4), 412-420. https://doi.org/10.1038/nm.4054
Ikeda, K., Kang, Q., Yoneshiro, T., Camporez, J. P., Maki, H., Homma, M., Shinoda, K., Chen, Y., Lu, X., Maretich, P., Tajima, K., Ajuwon, K. M., Okada, T., & Kajimura, S. (2017). UCP1-independent signaling involving SERCA2b-mediated calcium cycling regulates beige fat thermogenesis and systemic glucose homeostasis. Nature Medicine, 23(12), 1454-1465. https://doi.org/10.1038/nm.4429
Jin, L., Bian, X., Dong, W., Yang, R., Jing, C., Li, X., Yang, D., Guo, C., & Gao, W. (2022). A Chinese herbs complex ameliorates gut microbiota dysbiosis induced by intermittent cold exposure in female rats. Frontiers in Microbiology, 13, 1065780. https://doi.org/10.3389/fmicb.2022.1065780
Johnson, J. D., Campisi, J., Sharkey, C. M., Kennedy, S. L., Nickerson, M., Greenwood, B. N., & Fleshner, M. (2005). Catecholamines mediate stress-induced increases in peripheral and central inflammatory cytokines. Neuroscience, 135(4), 1295-1307. https://doi.org/10.1016/j.neuroscience.2005.06.090
Khakisahneh, S., Zhang, X., Nouri, Z., & Wang, D. (2020). Gut microbiota and host thermoregulation in response to ambient temperature fluctuations. mSystems, 5(4), e00514-20. https://doi.org/10.1128/mSystems.00514-20
Kim, Y. H., Yan, S., Fang, N., Zhang, Y., Zhang, S., Li, L., Wang, Z., Wang, K., Hou, T., Ji, X., Liang, Q., Duan, Y., Jiang, X., Gao, Q., Xu, W., Hao, H., Zhao, X., Han, X., Luo, Y., & Li, Y. (2024). Gut microbiota-derived leucine promotes cold-induced atherosclerosis by inhibiting macrophage efferocytosis. Research Square. https://doi.org/10.21203/rs.3.rs-4666347/v1
King, K. E., McCormick, J. J., & Kenny, G. P. (2023). Temperature-dependent relationship of autophagy and apoptotic signaling during cold-water immersion in young and older males. Advanced Biology, 7(12), e2300560. https://doi.org/10.1002/adbi.202300560
King, K. E., McCormick, J. J., Janetos, K. T., Goulet, N., Tetzlaff, E. J., & Kenny, G. P. (2023). Characterizing autophagic and apoptotic responses to cold stress in healthy, young and older men. Medicine & Science in Sports & Exercise, 55(9S), 113-114. https://doi.org/10.1249/01.mss.0000980756.89099.87
King, K. E., McCormick, J. J., McManus, M. K., Janetos, K. T., Goulet, N., & Kenny, G. P. (2024). Impaired autophagy following ex vivo cooling of simulated hypothermic temperatures in peripheral blood mononuclear cells from young and older adults. Journal of Thermal Biology, 121, 103831. https://doi.org/10.1016/j.jtherbio.2024.103831
Kozak, W., Conn, C. A., & Kluger, M. J. (1994). Lipopolysaccharide induces fever and depresses locomotor activity in unrestrained mice. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 266(1), R125-R135. https://doi.org/10.1152/ajpregu.1994.266.1.R125
LeBlanc, J., & Labrie, A. (1981). Glycogen and nonspecific adaptation to cold. Journal of Applied Physiology, 51(6), 1428-1432. https://doi.org/10.1152/jappl.1981.51.6.1428
Li, J., Cui, Z., Wei, M., Almutairi, M., & Yan, P. (2023). Omics analysis of the effect of cold normal saline stress through gastric gavage on LPS induced mice. Frontiers in Microbiology, 14, 1256748. https://doi.org/10.3389/fmicb.2023.1256748
Liu, J., Peng, F., Cheng, H., Zhang, D., Zhang, Y., Wang, L., Tang, F., Wang, J., Wan, Y., Wu, J., Zhou, Y., Feng, W., & Peng, C. (2023). Chronic cold environment regulates rheumatoid arthritis through modulation of gut microbiota-derived bile acids. Science of The Total Environment, 904, 166837. https://doi.org/10.1016/j.scitotenv.2023.166837
Liu, X., Li, S., Zhao, N., Xing, L., Gong, R., Li, T., Zhang, S., Li, J., & Bao, J. (2022). Effects of acute cold stress after intermittent cold stimulation on immune-related molecules, intestinal barrier genes, and heat shock proteins in broiler ileum. Animals, 12(23), 3260. https://doi.org/10.3390/ani12233260
Liu, Y., Zhou, E., Yu, Y., Wang, B., Zhang, L., Lei, R., Xue, B., Tian, X., Niu, J., Liu, J., Zhang, K., & Luo, B. (2024). Butyrate attenuates cold-induced hypertension via gut microbiota and activation of brown adipose tissue. Science of The Total Environment, 928, 173835. https://doi.org/10.1016/j.scitotenv.2024.173835
Lowell, B. B., & Spiegelman, B. M. (2000). Towards a molecular understanding of adaptive thermogenesis. Nature, 404(6778), 652-660. https://doi.org/10.1038/35007527
Luo, T., Zhu, J., Li, K., Li, Y., Li, J., Chen, Y., & Shi, H. (2024). Crosstalk between innate immunity and rumen-fecal microbiota under the cold stress in goats. Frontiers in Immunology, 15, 1363664. https://doi.org/10.3389/fimmu.2024.1363664
Lv, H., Xia, S., He, Y., Qiao, C., Liu, J., Guo, J., & Li, S. (2023). Effect of chronic cold stress on gut microbial diversity, intestinal inflammation and pyroptosis in mice. Research Square. https://doi.org/10.21203/rs.3.rs-3748421/v1
Lyte, J. M., Eckenberger, J., Keane, J., Robinson, K., Bacon, T., Assumpcao, A. L. F. V., Donoghue, A. M., Liyanage, R., Daniels, K. M., Caputi, V., & Lyte, M. (2024). Cold stress initiates catecholaminergic and serotonergic responses in the chicken gut that are associated with functional shifts in the microbiome. Poultry Science, 103(3), 103393. https://doi.org/10.1016/j.psj.2023.103393
Makinen, T. M. (2007). Human cold exposure, adaptation, and performance in high latitude environments. American Journal of Human Biology, 19(2), 155-164. https://doi.org/10.1002/ajhb.20627
Meng, Y., Chen, L., Lin, W., Wang, H., Xu, G., & Weng, X. (2020). Exercise reverses the alterations in gut microbiota upon cold exposure and promotes cold-induced weight loss. Frontiers in Physiology, 11, 311. https://doi.org/10.3389/fphys.2020.00311
Morrison, S. F., & Nakamura, K. (2011). Central neural pathways defining thermoregulation. Frontiers in Bioscience, 16(1), 74-104. https://doi.org/10.2741/3677
Mourtzoukou, E. G., & Falagas, M. E. (2007). Exposure to cold and respiratory tract infections. International Journal of Tuberculosis and Lung Disease, 11(9), 938-943.
Nakamura, K., & Morrison, S. F. (2008). A thermosensory pathway that controls body temperature. Nature Neuroscience, 11(1), 62-71. https://doi.org/10.1038/nn2027
Nedergaard, J., Bengtsson, T., & Cannon, B. (2007). Unexpected evidence for active brown adipose tissue in adult humans. American Journal of Physiology-Endocrinology and Metabolism, 293(2), E444-E452. https://doi.org/10.1152/ajpendo.00691.2006
Nicholls, D. G., & Locke, R. M. (1984). Thermogenic mechanisms in brown fat. Physiological Reviews, 64(1), 1-64. https://doi.org/10.1152/physrev.1984.64.1.1
Ouellet, V., Routhier-Labadie, A., Bellemare, W., Lakhal-Chaieb, L., Turcotte, E., Carpentier, A. C., & Richard, D. (2011). Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. Journal of Clinical Endocrinology & Metabolism, 96(1), 192-199. https://doi.org/10.1210/jc.2010-0989
Palou, A., Picó, C., Bonet, M. L., & Oliver, P. (1998). The uncoupling protein, thermogenin. International Journal of Biochemistry & Cell Biology, 30(1), 7-11. https://doi.org/10.1016/S1357-2725(97)00065-X
Pénicaud, L., Cousin, B., Leloup, C., Lorsignol, A., & Casteilla, L. (2000). The autonomic nervous system, adipose tissue plasticity, and energy balance. Nutrition, 16(10), 903-908. https://doi.org/10.1016/S0899-9007(00)00414-8
Pongor, V., Toldi, G., Szabó, M., Vásárhelyi, B., & Vásárhelyi, B. (2011). Systemic and immunomodulatory effects of whole body therapeutic hypothermia. Orvosi Hetilap, 152(15), 575-580. https://doi.org/10.1556/OH.2011.29086
Romanovsky, A. A. (2007). Thermoregulation: Some concepts have changed. Functional architecture of the thermoregulatory system. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 292(1), R37-R46. https://doi.org/10.1152/ajpregu.00668.2006
Saito, M., Okamatsu-Ogura, Y., Matsushita, M., Watanabe, K., Yoneshiro, T., Nio-Kobayashi, J., Iwanaga, T., Miyagawa, M., Kameya, T., Nakada, K., Kawai, Y., & Tsujisaki, M. (2009). High incidence of metabolically active brown adipose tissue in healthy adult humans: Effects of cold exposure and adiposity. Diabetes, 58(7), 1526-1531. https://doi.org/10.2337/db09-0530
Salikova, S. P., Vlasov, A. A., & Grinevich, V. B. (2021). Human adaptation to the conditions of the far north: Emphasis on the correction of the microbial-tissue complex of the gastrointestinal tract. Human Ecology, 2, 4-12.
Seale, P., Bjork, B., Yang, W., Kajimura, S., Chin, S., Kuang, S., Scimè, A., Devarakonda, S., Conroe, H. M., Erdjument-Bromage, H., Tempst, P., Rudnicki, M. A., Beier, D. R., & Spiegelman, B. M. (2008). PRDM16 controls a brown fat/skeletal muscle switch. Nature, 454(7207), 961-967. https://doi.org/10.1038/nature07182
Shi, H., Kokoeva, M. V., Inouye, K., Tzameli, I., Yin, H., & Flier, J. S. (2006). TLR4 links innate immunity and fatty acid-induced insulin resistance. Journal of Clinical Investigation, 116(11), 3015-3025. https://doi.org/10.1172/JCI28898
Sidossis, L., & Kajimura, S. (2015). Brown and beige fat in humans: Thermogenic adipocytes that control energy and glucose homeostasis. Journal of Clinical Investigation, 125(2), 478-486. https://doi.org/10.1172/JCI78362
Soare, A., Weiss, E. P., & Pozzilli, P. (2014). Benefits of caloric restriction for cardiometabolic health, including type 2 diabetes mellitus risk. Diabetes/Metabolism Research and Reviews, 30(S1), 41-47. https://doi.org/10.1002/dmrr.2517
Srivastava, S., Baxa, U., Niu, G., Chen, X., & Veech, R. L. (2013). A ketogenic diet increases brown adipose tissue mitochondrial proteins and UCP1 levels in mice. IUBMB Life, 65(1), 58-66. https://doi.org/10.1002/iub.1102
Stanford, K. I., Middelbeek, R. J., Townsend, K. L., An, D., Nygaard, E. B., Hitchcox, K. M., Markan, K. R., Nakano, K., Hirshman, M. F., Tseng, Y. H., & Goodyear, L. J. (2013). Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. Journal of Clinical Investigation, 123(1), 215-223. https://doi.org/10.1172/JCI62308
Straat, M. E., Martinez-Tellez, B., Mishre, A. S. S., Verkleij, M. M. A., Kemmeren, M., Pelsma, I. C. M., Alcantara, J. M. A., Gutierrez, A. M., Kooijman, S., Boon, M. R., & Rensen, P. C. (2022). Cold-induced thermogenesis shows a diurnal variation that unfolds differently in males and females. The Journal of Clinical Endocrinology & Metabolism, 107(6), 1626-1635. https://doi.org/10.1210/clinem/dgac094
Sun, L., Wang, X., Zou, Y., He, Y., Li, J., Li, P., & Zhang, J. (2023). Cold stress induces colitis-like phenotypes in mice by altering gut microbiota and metabolites. Frontiers in Microbiology, 14, Article 1134246. https://doi.org/10.3389/fmicb.2023.1134246
Tan, C. L., & Knight, Z. A. (2018). Regulation of body temperature by the nervous system. Neuron, 98(1), 31-48. https://doi.org/10.1016/j.neuron.2018.02.022
Timmons, J. A., Wennmalm, K., Larsson, O., Walden, T. B., Lassmann, T., Petrovic, N., Hamilton, D. L., Gimeno, R. E., Wahlestedt, C., Baar, K., Nedergaard, J., & Cannon, B. (2007). Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proceedings of the National Academy of Sciences, 104(11), 4401-4406. https://doi.org/10.1073/pnas.0610615104
Tschöp, M. H., Speakman, J. R., Arch, J. R., Auwerx, J., Brüning, J. C., Chan, L., Eckel, R. H., Farese Jr, R. V., Galgani, J. E., Hambly, C., Herman, M. A., Horvath, T. L., Kahn, B. B., Kozma, S. C., Maratos-Flier, E., Müller, T. D., Münzberg, H., Pfluger, P. T., Plum, L., & Ravussin, E. (2012). A guide to analysis of mouse energy metabolism. Nature Methods, 9(1), 57-63. https://doi.org/10.1038/nmeth.1806
van Marken Lichtenbelt, W. D., Vanhommerig, J. W., Smulders, N. M., Drossaerts, J. M., Kemerink, G. J., Bouvy, N. D., Schrauwen, P., & Teule, G. J. (2009). Cold-activated brown adipose tissue in healthy men. New England Journal of Medicine, 360(15), 1500-1508. https://doi.org/10.1056/NEJMoa0808718
Vašek, D., Holíček, P., Galatik, F., Kratochvilova, A., Porubská, B., Somova, V., Fikarová, N., Hájková, M., Převorovský, M., Žurmanová, J., & Krulová, M. (2024). Immune response to cold exposure: Role of γδ T cells and TLR2‐mediated inflammation. European Journal of Immunology, 54(8), Article 2350897. https://doi.org/10.1002/eji.202350897
Virtanen, K. A., Lidell, M. E., Orava, J., Heglind, M., Westergren, R., Niemi, T., Taittonen, M., Laine, J., Savisto, N. J., Enerbäck, S., & Nuutila, P. (2009). Functional brown adipose tissue in healthy adults. New England Journal of Medicine, 360(15), 1518-1525. https://doi.org/10.1056/NEJMoa0808949
Wang, Z., Wu, Y., Li, X., & Liu, W. (2024). The gut microbiota facilitate their host tolerance to extreme temperatures. BMC Microbiology, 24, Article 277. https://doi.org/10.1186/s12866-024-03277-6
Wei, W., Zhang, G., Zhang, Y., Zhang, L., Wu, S., Li, X., & Yang, D. (2023). Research progress on adaptive modifications of the gut microflora and regulation of host glucose and lipid metabolism by cold stimulation. Frigid Zone Medicine, 3(1), 13-21. https://doi.org/10.2478/fzm-2023-0003
Worthmann, A., John, C., Rühlemann, M. C., Baguhl, M., Heinsen, F., Schaltenberg, N., Heine, M., Schlein, C., Evangelakos, I., Mineo, C., Fischer, M., Dandri, M., Kremoser, C., Scheja, L., Franke, A., Shaul, P. W., & Heeren, J. (2017). Cold-induced conversion of cholesterol to bile acids in mice shapes the gut microbiome and promotes adaptive thermogenesis. Nature Medicine, 23(7), 839-849. https://doi.org/10.1038/nm.4357
Wu, G., Zhang, Y., Zheng, N., Tian, S., Liao, J., Le, W., Li, H., & Zhang, W. (2023). Cold exposure promotes coronavirus infection by altering the gut microbiota and lipid metabolism to reduce host immunity. Frigid Zone Medicine, 1(4), 219-229. https://doi.org/10.2478/fzm-2023-0029
Wu, J., Boström, P., Sparks, L. M., Ye, L., Choi, J. H., Giang, A. H., Khandekar, M., Virtanen, K. A., Nuutila, P., Schaart, G., Huang, K., Tu, H., van Marken Lichtenbelt, W. D., Hoeks, J., Enerbäck, S., Schrauwen, P., & Spiegelman, B. M. (2012). Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell, 150(2), 366-376. https://doi.org/10.1016/j.cell.2012.05.016
Wu, Y., Deng, N., Liu, J., Jiang, P., & Tan, Z. (2023). Alterations in intestinal microbiota and enzyme activities under cold-humid stress: Implications for diarrhea in cold-dampness trapped spleen syndrome. Frontiers in Microbiology, 14, Article 1288430. https://doi.org/10.3389/fmicb.2023.1288430
Ye, Y., Wang, H., Chen, W., Chen, Z., Wu, D., Zhang, F., & Hu, F. (2024). Dynamic changes of immunocyte subpopulations in thermogenic activation of adipose tissues. Frontiers in Immunology, 15, Article 1375138. https://doi.org/10.3389/fimmu.2024.1375138
Yoneshiro, T., Aita, S., Matsushita, M., Kayahara, T., Kameya, T., Kawai, Y., Iwanaga, T., & Saito, M. (2013). Recruited brown adipose tissue as an antiobesity agent in humans. Journal of Clinical Investigation, 123(8), 3404-3408. https://doi.org/10.1172/JCI67803
Young, P., Arch, J. R., & Ashwell, M. (1984). Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Letters, 167(1), 10-14. https://doi.org/10.1016/0014-5793(84)80822-4
Zhang, C., Peng, X., Wu, Y., Peng, M., Liu, T., & Tan, Z. (2023). Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice. Research Square. https://doi.org/10.21203/rs.3.rs-3431725/v1
Zhang, C., Peng, X., Wu, Y., Peng, M., Liu, T., & Tan, Z. (2024). Intestinal mucosal microbiota mediate amino acid metabolism involved in the gastrointestinal adaptability to cold and humid environmental stress in mice. Microbial Cell Factories, 23, Article 307. https://doi.org/10.1186/s12934-024-02307-2
Zhang, S., Li, Y., Wang, J., Zhu, R., Sun, L., & Mi, J. (2024). Cold stress changes the composition and function of microbiota in the content and mucosa of the ileum and colon in piglets. Animal Production Science, 64(8), Article AN23374. https://doi.org/10.1071/an23374
Zhang, X., & Wang, D. (2022). Gut microbial community and host thermoregulation in small mammals. Frontiers in Physiology, 13, Article 888324. https://doi.org/10.3389/fphys.2022.888324
Zhang, X., Sukhchuluun, G., Bo, T., Chi, Q., Yang, J., Chen, B., Zhang, L., & Wang, D. (2018). Huddling remodels gut microbiota to reduce energy requirements in a small mammal species during cold exposure. Microbiome, 6, Article 473. https://doi.org/10.1186/s40168-018-0473-9
Zhang, Y., Sun, L., Zhu, R., Zhang, S., Liu, S., Wang, Y., Wu, Y., Xing, S., Liao, X., & Mi, J. (2022). Porcine gut microbiota in mediating host metabolic adaptation to cold stress. npj Biofilms and Microbiomes, 8, Article 283. https://doi.org/10.1038/s41522-022-00283-2
Zhou, E., He, L., Xiao, Y., Zhang, K., & Luo, B. (2024). Cold exposure, gut microbiota and health implications: A narrative review. Science of Total Environment, 912, Article 170060. https://doi.org/10.1016/j.scitotenv.2024.170060
Zingaretti, M. C., Crosta, F., Vitali, A., Guerrieri, M., Frontini, A., Cannon, B., Nedergaard, J., & Cinti, S. (2009). The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. The FASEB Journal, 23(9), 3113-3120. https://doi.org/10.1096/fj.09-133546
Zwaag, J., Naaktgeboren, R., Herwaarden, A. E. V., Pickkers, P., & Kox, M. (2020). The combination of cold exposure training and a breathing exercise attenuates the inflammatory response in humans. Research Square. https://doi.org/10.21203/rs.2.20192/v1
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2025 Anatoliy Gozhenko, Walery Zukow, Olena Gozhenko, Oleksandr Vitiukov
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 257
Number of citations: 0
