The DOI matches its Crossref record; 94 of the 99 references it cites were found in a registry or an index.
Nonshivering thermogenesis and its adequate measurement in metabolic studies
Open accessAbstract
Alterations in nonshivering thermogenesis are presently discussed as being both potentially causative of and able to counteract obesity. However, the necessity for mammals to defend their body temperature means that the ambient temperature profoundly affects the outcome and interpretation of metabolic experiments. An adequate understanding and assessment of nonshivering thermogenesis is therefore paramount for metabolic studies. Classical nonshivering thermogenesis is facultative, i.e. it is only activated when an animal acutely requires extra heat (switched on in minutes), and adaptive, i.e. it takes weeks for an increase in capacity to develop. Nonshivering thermogenesis is fully due to brown adipose tissue activity; adaptation corresponds to the recruitment of this tissue. Diet-induced thermogenesis is probably also facultative and adaptive and due to brown adipose tissue activity. Although all mammals respond to injected/infused norepinephrine (noradrenaline) with an increase in metabolism, in non-adapted mammals this increase mainly represents the response of organs not involved in nonshivering thermogenesis; only the increase after adaptation represents nonshivering thermogenesis. Thermogenesis (metabolism) should be expressed per animal, and not per body mass [not even to any power (0.75 or 0.66)]. A 'cold tolerance test' does not examine nonshivering thermogenesis capacity; rather it tests shivering capacity and endurance. For mice, normal animal house temperatures are markedly below thermoneutrality, and the mice therefore have a metabolic rate and food consumption about 1.5 times higher than their intrinsic requirements. Housing and examining mice at normal house temperatures carries a high risk of identifying false positives for intrinsic metabolic changes; in particular, mutations/treatments that affect the animal's insulation (fur, skin) may lead to such problems. Correspondingly, true alterations in intrinsic metabolic rate remain undetected when metabolism is examined at temperatures below thermoneutrality. Thus, experiments with animals kept and examined at thermoneutrality are likely to yield an improved possibility of identifying agents and genes important for human energy balance.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Animal models have shown that GLP-1 can increase energy expenditure and regulate heat production and conversion from white adipose tissue to brown adipose tissue in obese mice [42], although human data on this effect are not yet convincing [18,43].”
From New Developments in Pharmacological Treatment of Obesity and Type 2 Diabetes—Beyond and within GLP-1 Receptor Agonists (2024) · cites this paper as [42]
Citations
Cites
Brown Adipose Tissue: Function and Physiological Significance
CANNON, B., & NEDERGAARD, J. (2004) · Physiological Reviews · doi:10.1152/physrev.00015.2003 · Cited by 6,433
Self-citationAnimal Physiology: Adaptation and Environment
Schmidt‐Nielsen, K. (1962) · Cited by 2,489
Unexpected evidence for active brown adipose tissue in adult humans
Nedergaard, J., Bengtsson, T., & Cannon, B. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00691.2006 · Cited by 1,824
Self-citationA role for brown adipose tissue in diet-induced thermogenesis
Rothwell, N. J., & Stock, M. J. (1979) · Nature · doi:10.1038/281031a0 · Cited by 1,606
The menthol receptor TRPM8 is the principal detector of environmental cold
Bautista, D. M., Siemens, J., Glazer, J. M., Tsuruda, P. R., Basbaum, A. I., Stucky, C. L., Jordt, S. E., & Julius, D. J. (2007) · Nature · doi:10.1038/nature05910 · Cited by 1,392
Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese
Enerbäck, S., Jacobsson, A., Simpson, E. M., Guerra, C., Yamashita, H., Harper, M.-E., & Kozak, L. P. (1997) · Nature · doi:10.1038/387090a0 · Cited by 1,379
Feldmann, H. M., Golozoubova, V., Cannon, B., & Nedergaard, J. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.12.014 · Cited by 1,318
Self-citationPetrovic, N., Walden, T. B., Shabalina, I. G., Timmons, J. A., Cannon, B., & Nedergaard, J. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.053942 · Cited by 1,263
Self-citationLoss of stearoyl–CoA desaturase-1 function protects mice against adiposity
Ntambi, J. M., Miyazaki, M., Stoehr, J. P., Hong, L., Kendziorski, C. M., Yandell, B. S., Song, Y., Cohen, P., Friedman, J. M., & Attie, A. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.132384699 · Cited by 1,096
Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat
Smith, S. J., Cases, S., Jensen, D. R., Chen, H. C., Sande, E., Tow, B., Sanan, D. A., Raber, J., Eckel, R. H., & Farese, R. V. (2000) · Nature Genetics · doi:10.1038/75651 · Cited by 895
Research works printed but not linked: 2
- Feldmann, 2010, Brown adipose tissue is essential for diet-induced obesity: the absence of UCP1 makes the obesity-resistant 129Sv mouse obesity-prone, due to lack of adaptive adrenergic thermogenesis, Obesity Rev., 11, 92
- Smith, 1961, Thermogenic activity of the hibernating gland in the cold-acclimated rat, Physiologist, 4, 113
Cited by
Sorted by citations
Glucagon-like peptide 1 (GLP-1)
Müller, T. D., Finan, B., Bloom, S. R., D'Alessio, D., Drucker, D. J., Flatt, P. R., Fritsche, A., Gribble, F., Grill, H. J., Habener, J. F., et al. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.09.010 · Cited by 1,868
“In mice, acute central (i.c.v.) but not peripheral administration of GLP-1 increased brown adipose tissue (BAT) temperature and increased the activity of sympathetic fibers that innervate the inguinal BAT [773].”
BackgroundInfluentialFGF21 regulates PGC-1α and browning of white adipose tissues in adaptive thermogenesis
Fisher, F. M., Kleiner, S., Douris, N., Fox, E. C., Mepani, R. J., Verdeguer, F., Wu, J., Kharitonenkov, A., Flier, J. S., Maratos-Flier, E., et al. (2012) · Genes & Development · doi:10.1101/gad.177857.111 · Cited by 1,478
“2A,B), which is indicative of enhanced shivering (Cannon and Nedergaard 2011).”
BackgroundSarcopenic obesity in older adults: aetiology, epidemiology and treatment strategies
Batsis, J. A., & Villareal, D. T. (2018) · Nature Reviews Endocrinology · doi:10.1038/s41574-018-0062-9 · Cited by 1,382
Fever and the thermal regulation of immunity: the immune system feels the heat
Evans, S. S., Repasky, E. A., & Fisher, D. T. (2015) · Nature reviews. Immunology · doi:10.1038/nri3843 · Cited by 1,312
Alternatively activated macrophages produce catecholamines to sustain adaptive thermogenesis
Nguyen, K. D., Qiu, Y., Cui, X., Goh, Y. P. S., Mwangi, J., David, T., Mukundan, L., Brombacher, F., Locksley, R. M., & Chawla, A. (2011) · Nature · doi:10.1038/nature10653 · Cited by 1,038
Qiu, Y., Nguyen, K. D., Odegaard, J. I., Cui, X., Tian, X., Locksley, R. M., Palmiter, R. D., & Chawla, A. (2014) · Cell · doi:10.1016/j.cell.2014.03.066 · Cited by 888
Protection from obesity and diabetes by blockade of TGF-β/smad3 signaling
Yadav, H., Quijano, C., Kamaraju, A. K., Gavrilova, O., Malek, R., Chen, W., Zerfas, P., Zhigang, D., Wright, E. C., Stuelten, C., et al. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.04.013 · Cited by 709
“In contrast, UCP1+ cells were absent in Smad3+/+ WAT.”
BackgroundInfluentialActivated Type 2 Innate Lymphoid Cells Regulate Beige Fat Biogenesis
Lee, M.-W., Odegaard, J. I., Mukundan, L., Qiu, Y., Molofsky, A. B., Nussbaum, J. C., Yun, K. M., Locksley, R. M., & Chawla, A. (2014) · Cell · doi:10.1016/j.cell.2014.12.011 · Cited by 680
“This rapid increase in heat production, which occurs within seconds to minutes, is mediated by several thermoeffectors, including cutaneous vasoconstriction, skeletal muscle shivering, and UCP1-mediated respiration in brown adipocytes; processes that are all activated by the sympathetic nervous system (Cannon and Nede…”
Cypess, A. M., White, A. P., Vernochet, C., Schulz, T. J., Xue, R., Sass, C. A., Huang, T. L., Roberts‐Toler, C., Weiner, L. S., Sze, C., et al. (2013) · Nature Medicine · doi:10.1038/nm.3112 · Cited by 683
Li, G., Xie, C., Lu, S., Nichols, R. G., Tian, Y., Li, L., Patel, D., Ma, Y., Brocker, C. N., Yan, T., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.08.019 · Cited by 667
Accumulation of succinate controls activation of adipose tissue thermogenesis
Mills, E. L., Pierce, K. A., Jedrychowski, M. P., Garrity, R., Winther, S., Vidoni, S., Yoneshiro, T., Spinelli, J. B., Lu, G. Z., Kazak, L., et al. (2018) · Nature · doi:10.1038/s41586-018-0353-2 · Cited by 539
The Browning of White Adipose Tissue: Some Burning Issues
Nedergaard, J., & Cannon, B. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.07.005 · Cited by 509
Self-citationDecreased consumption of branched-chain amino acids improves metabolic health
Fontana, L., Cummings, N. E., Arriola Apelo, S. I., Neuman, J. C., Kasza, I., Schmidt, B. A., Cava, E., Spelta, F., Tosti, V., Syed, F. A., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.092 · Cited by 466
“, 2006), we observed increased intradermal adipose tissue, which has been proposed to be key to thermal insulation (Cannon and Nedergaard, 2011; Kasza et al., 2014).”
Mitochondrial ROS regulate thermogenic energy expenditure and sulfenylation of UCP1
Chouchani, E. T., Kazak, L., Jedrychowski, M. P., Lu, G. Z., Erickson, B. K., Szpyt, J., Pierce, K. A., Laznik-Bogoslavski, D., Vetrivelan, R., Clish, C. B., et al. (2016) · Nature · doi:10.1038/nature17399 · Cited by 469
How May GIP Enhance the Therapeutic Efficacy of GLP-1?
Samms, R. J., Coghlan, M. P., & Sloop, K. W. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2020.02.006 · Cited by 419
Prdm16 Is Required for the Maintenance of Brown Adipocyte Identity and Function in Adult Mice
Harms, M., Ishibashi, J., Wang, W., Lim, H., Goyama, S., Sato, T., Kurokawa, M., Won, K., & Seale, P. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.03.007 · Cited by 393
“Since mice rely substantially on shivering thermogenesis during acute cold exposure (Cannon and Nedergaard, 2011), we further analyzed in vivo BAT function by measuring whole-animal oxygen consumption before and at several time points after injection of norepinephrine (NE), the classic activator of…”
BackgroundMethodInfluentialBrown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat
Schulz, T. J., Huang, P. C., Huang, T. L., Xue, R., McDougall, L. E., Townsend, K. L., Cypess, A. M., Mishina, Y. M., Gussoni, E., & Tseng, Y. (2013) · Nature · doi:10.1038/nature11943 · Cited by 389
EHMT1 controls brown adipose cell fate and thermogenesis through the PRDM16 complex
Ohno, H., Shinoda, K., Ohyama, K., Sharp, L. Z., & Kajimura, S. (2013) · Nature · doi:10.1038/nature12652 · Cited by 334
Schreiber, R., Diwoky, C., Schoiswohl, G., Feiler, U., Wongsiriroj, N., Abdellatif, M., Kolb, D., Hoeks, J., Kershaw, E. E., Sedej, S., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.09.004 · Cited by 334
“Cell Metabolism 26, 1–11, N This is an open access article under the CC BY-N chain (Cannon and Nedergaard, 2011; Fedorenko et al., 2012).”
BackgroundCold but not sympathomimetics activates human brown adipose tissue in vivo
Cypess, A. M., Chen, Y., Sze, C., Wang, K., English, J., Chan, O., Holman, A. R., Tal, I., Palmer, M. R., Kolodny, G. M., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207911109 · Cited by 312
“In addition to generating heat via nonshivering thermogenesis, BAT also burns calories in rodents through a process known as diet-induced thermogenesis (19, 20), indicating that despite its relatively small size, BAT could play a prominent role in general metabolic homeostasis.”
BackgroundThermal physiology of laboratory mice: Defining thermoneutrality
Gordon, C. J. (2012) · Journal of Thermal Biology · doi:10.1016/j.jtherbio.2012.08.004 · Cited by 305
Mfn2 is critical for brown adipose tissue thermogenic function
Boutant, M., Kulkarni, S. S., Joffraud, M., Ratajczak, J., Valera‐Alberni, M., Combe, R., Antonio Zorzano, A., & Cantó, C. (2017) · The EMBO Journal · doi:10.15252/embj.201694914 · Cited by 309
“In order to evaluate non-shivering thermogenesis (BAT function), we measured is whole-body O 2 consumption in response to a specific b 3-adrenergic agonist, CL, in anesthetized mice as previously described (Cannon & Nedergaard, 2011).”
Vanweert, F., Schrauwen, P., & Phielix, E. (2022) · Nutrition and Diabetes · doi:10.1038/s41387-022-00213-3 · Cited by 331
Development of insulin resistance in mice lacking PGC-1α in adipose tissues
Kleiner, S., Mepani, R. J., Laznik, D., Li, Y., Jurczak, M. J., Jornayvaz, F. R., Estall, J. L., Bhowmick, D. C., Shulman, G. I., & Spiegelman, B. M. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207287109 · Cited by 291
“This phenotypemay depend on the housing of animals at ambient temperature (21 °C), which could be considered a mild thermogenic stress (42); it was not observed in WAT in a different mouse model of adipose PGC-1α deficiency in which mice were housed at thermoneutrality (43).”
BackgroundEnergetic Trade-Offs and Hypometabolic States Promote Disease Tolerance
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) · Cell · doi:10.1016/j.cell.2019.01.050 · Cited by 286
miR-155 regulates differentiation of brown and beige adipocytes via a bistable circuit
Chen, Y., Siegel, F., Kipschull, S., Haas, B., Fröhlich, H., Meister, G., & Pfeifer, A. (2013) · Nature Communications · doi:10.1038/ncomms2742 · Cited by 282
Fischer, A. W., Cannon, B., & Nedergaard, J. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.10.009 · Cited by 282
Self-citationInhibition of Notch signaling promotes browning of white adipose tissue and ameliorates obesity
Bi, P., Shan, T., Liu, W., Yue, F., Yang, X., Liang, X.-R., Wang, J., Li, J., Carlesso, N., Liu, X., et al. (2014) · Nature Medicine · doi:10.1038/nm.3615 · Cited by 271
Measuring Energy Metabolism in the Mouse – Theoretical, Practical, and Analytical Considerations
Speakman, J. R. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2013.00034 · Cited by 268
“The procedure for the NA test of non-shivering thermogenesis is described in Cannon and Nedergaard (2011) and briefly summarized as follows.”
BackgroundMethodInfluentialCreatine metabolism: energy homeostasis, immunity and cancer biology
Kazak, L., & Cohen, P. (2020) · Nature Reviews Endocrinology · doi:10.1038/s41574-020-0365-5 · Cited by 267
Genetically encoded fluorescent thermosensors visualize subcellular thermoregulation in living cells
Kiyonaka, S., Kajimoto, T., Sakaguchi, R., Shinmi, D., Omatsu‐Kanbe, M., Matsuura, H., Imamura, H., Yoshizaki, T., Hamachi, I., Morii, T., et al. (2013) · Nature Methods · doi:10.1038/nmeth.2690 · Cited by 263
The nuclear receptor Rev-erbα controls circadian thermogenic plasticity
Gerhart‐Hines, Z., Feng, D., Emmett, M. J., Everett, L. J., Loro, E., Briggs, E. R., Bugge, A. K., Hou, C., Ferrara, C., Seale, P., et al. (2013) · Nature · doi:10.1038/nature12642 · Cited by 265
GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice
Samms, R. J., Christe, M. E., Collins, K. A. L., Pirro, V., Droz, B. A., Holland, A. K., Friedrich, J. L., Wojnicki, S., Konkol, D. L., Cosgrove, R., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci146353 · Cited by 256
“Thus, to maximize weight gain, circumvent protection from obesity, and ensure a state of IR, we exposed Glp-1r–/– animals to a 60% HFD and minimized thermal stress by housing animals in a thermal neutral (27°C) environment (38).”
BackgroundMechanisms of insulin resistance related to white, beige, and brown adipocytes
Czech, M. (2020) · Molecular Metabolism · doi:10.1016/j.molmet.2019.12.014 · Cited by 258
Even, P. C., & Nadkarni, N. A. (2012) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00137.2012 · Cited by 246
Warming the mouse to model human diseases
Ganeshan, K., & Chawla, A. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.48 · Cited by 222
Integration of body temperature into the analysis of energy expenditure in the mouse
Abreu-Vieira, G., Xiao, C., Gavrilova, O., & Reitman, M. L. (2015) · Molecular Metabolism · doi:10.1016/j.molmet.2015.03.001 · Cited by 225
“Mice are typically studied below their thermoneutral zone [7,8].”
BackgroundEmerging Complexities in Adipocyte Origins and Identity
Sánchez-Gurmaches, J., Hung, C., & Guertin, D. A. (2016) · Trends in Cell Biology · doi:10.1016/j.tcb.2016.01.004 · Cited by 225
“At 22°C, mice are cold stressed and have an approximately 50% higher metabolic rate and consume more food than at thermoneutrality [92].”
BackgroundThe Immune System as a Sensor of the Metabolic State
Odegaard, J. I., & Chawla, A. (2013) · Immunity · doi:10.1016/j.immuni.2013.04.001 · Cited by 219
“In mammals, thermoregulation is composed of both heat-loss-reducing strategies (such as piloerection and cold-aversion behavior) and heat-generating strategies, of which nonshivering thermogenesis is the most important (Cannon and Nedergaard, 2011; Lowell and Spiegelman, 2000; Tseng et al., 2010).”
Stearoyl-CoA desaturase: rogue or innocent bystander?
Hodson, L., & Fielding, B. A. (2012) · Progress in Lipid Research · doi:10.1016/j.plipres.2012.08.002 · Cited by 220
“The lack of weight gain is attributed to increased energy expenditure and oxygen consumption, which may in part be explained by alopecia, skin barrier abnormalities [29] thus making it difficult for the mouse to thermoregulate as thermoneutrality of Scd1 deficient mice would presumably be higher than wild type mice [2…”
BackgroundBianco, A. C., Anderson, G., Forrest, D., Galton, V. A., Gereben, B., Kim, B. W., Kopp, P. A., Liao, X. H., Obregon, M. J., Peeters, R. P., et al. (2014) · Thyroid · doi:10.1089/thy.2013.0109 · Cited by 205
Sánchez-Gurmaches, J., Tang, Y., Jespersen, N. Z., Wallace, M., Calejman, C. M., Gujja, S., Li, H., Edwards, Y. J. K., Wolfrum, C., Metallo, C. M., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.008 · Cited by 204
“However, studies using rodents often compare subcutaneouswhite adipose tissue (WAT) (andBAT) between animals housed at standardmouse facility temperature (often 21 C–22 C) and severe cold (SC) (typically 4 C–10 C), which induces ‘‘browning’’ of WAT, but also exposes mice to extreme conditions that may not be physiolog…”
InfluentialBrown adipose tissue thermogenic adaptation requires Nrf1-mediated proteasomal activity
Bartelt, A., Widenmaier, S. B., Schlein, C., Johann, K., Gonçalves, R. L. S., Eguchi, K., Fischer, A. W., Parlakgül, G., Snyder, N., Nguyen, T. B., et al. (2018) · Nature Medicine · doi:10.1038/nm.4481 · Cited by 212
Hypothalamic control of energy expenditure and thermogenesis
Tran, L. T., Park, S., Kim, S. K., Lee, J. S., Kim, K. W., & Kwon, O. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00741-z · Cited by 208
Brown Adipose Tissue in Adult Humans: A Metabolic Renaissance
Lee, P. C., Swarbrick, M. M., & Ho, K. K. Y. (2013) · Endocrine Reviews · doi:10.1210/er.2012-1081 · Cited by 224
Heat or Insulation: Behavioral Titration of Mouse Preference for Warmth or Access to a Nest
Gaskill, B. N., Gordon, C. J., Pajor, E. A., Lucas, J. R., Davis, J. K., & Garner, J. P. (2012) · PLoS ONE · doi:10.1371/journal.pone.0032799 · Cited by 204
“For instance, mice being housed at 26uC (the upper range of recommended temperatures) theoretically would need less material to stay warm than mice being housed at 20uC (the lower range) based on models of heat transfer [7].”
BackgroundInfluentialNot so hot: Optimal housing temperatures for mice to mimic the thermal environment of humans
Speakman, J. R., & Keijer, J. (2012) · Molecular Metabolism · doi:10.1016/j.molmet.2012.10.002 · Cited by 199
“The recommendation has therefore been made that studies of mice should optimally be made at 30 1C, within the mouse thermoneutral zone, to best facilitate comparisons to humans ([4,5,11,31,36]—but see [49] for some practical problems with this recommendation).”
BackgroundHistone deacetylase 3 prepares brown adipose tissue for acute thermogenic challenge
Emmett, M. J., Lim, H., Jager, J., Richter, H. J., Adlanmérini, M., Peed, L. C., Briggs, E. R., Steger, D. J., Ma, T., Sims, C. A., et al. (2017) · Nature · doi:10.1038/nature22819 · Cited by 200
“Following previously described protocols 33 , mice maintained at 22°C were anesthetized with 75 mg kg −1 pentobarbital (Nembutal) by intraperitoneal injection and placed into CLAMS cages pre-acclimated to 33°C to maintain mouse body temperature while under anesthesia.”
Impact of nesting material on mouse body temperature and physiology
Gaskill, B. N., Gordon, C. J., Pajor, E. A., Lucas, J. R., Davis, J. K., & Garner, J. P. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.12.018 · Cited by 189
Eng, J. W. ‐., Kokolus, K. M., Reed, C. B., Hylander, B. L., Ma, W. W., & Repasky, E. A. (2014) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-014-1617-9 · Cited by 197
“This process, mediated primarily by NE, facilitates a rapid rise in metabolic rate and an elevation in body temperature [18].”
BackgroundDai, N., Zhao, L., Wrighting, D., Krämer, D., Majithia, A., Wang, Y., Cracan, V., Borges-Rivera, D., Mootha, V. K., Nahrendorf, M., et al. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.03.006 · Cited by 188
“Mice maintained at 22 C–23 C, far from their thermoneutral temperature (28 C–30 C), are partially cold adapted, a response that involves increased mitochondrial biogenesis and UCP1 expression in brown fat (Cannon and Nedergaard, 2004, 2011).”
BackgroundResultInfluentialAdaptive thermogenesis with weight loss in humans
Müller, M. J., & Bosy‐Westphal, A. (2013) · Obesity · doi:10.1002/oby.20027 · Cited by 181
“Without adrenergic stimulation, there is neither uncoupling nor functional BAT-activity (4).”
BackgroundInfluentialMouse Thermoregulation: Introducing the Concept of the Thermoneutral Point
Škop, V., Guo, J., Liu, N., Xiao, C., Hall, K. D., Gavrilova, O., & Reitman, M. L. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.065 · Cited by 181
“Heat loss in the TNZ is controlled chiefly by regulating blood flow to superficial sites (Cannon and Nedergaard, 2011; Gordon, 2012; Kingma et al., 2012; Romanovsky, 2018; Romanovsky et al., 2002).”
BackgroundGenome-Wide Analysis of Cold Adaptation in Indigenous Siberian Populations
Cardona, A., Pagani, L., Antão, T., Lawson, D. J., Eichstaedt, C. A., Yngvadóttir, B., Shwe, M. T. T., Wee, J. T. S., Romero, I. G., Raj, S. M., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0098076 · Cited by 181
“Mechanisms allowing adaptation to the cold environment are expected to be complex and probably similar to convergent processes of high altitude adaptation [68] and therefore different cold-adapted populations may have undergone selection processes targeting different physiological functions [19,21].”
InfluentialBrown adipose tissue: Development, metabolism and beyond
Schulz, T. J., & Tseng, Y.-H. (2013) · Biochemical Journal · doi:10.1042/bj20130457 · Cited by 173
Chen, K. Y., Brychta, R. J., Linderman, J. D., Smith, S., Courville, A. B., Dieckmann, W., Herscovitch, P., Millo, C., Remaley, A. T., Lee, P., et al. (2013) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-4213 · Cited by 178
Tsoli, M., Moore, M. M., Burg, D. W., Painter, A., Taylor, R., Lockie, S. H., Turner, N. A., Warren, A., Cooney, G., Oldfield, B. J., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3536 · Cited by 174
“at uncovering a phenotype for UCP1 when mice were acclimated to normal animal housing temperatures (34).”
A liver stress-endocrine nexus promotes metabolic integrity during dietary protein dilution
Maida, A., Zota, A., Sjøberg, K. A., Schumacher, J., Sijmonsma, T. P., Pfenninger, A., Christensen, M. M., Gantert, T., Fuhrmeister, J., Rothermel, U., et al. (2016) · Journal of Clinical Investigation · doi:10.1172/jci85946 · Cited by 170
Of mice and men: The physiological role of adipose triglyceride lipase (ATGL)
Schreiber, R., Xie, H., & Schweiger, M. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2018.10.008 · Cited by 178
Translating Animal Model Research: Does It Matter That Our Rodents Are Cold?
Maloney, S. K., Fuller, A., Mitchell, D., Gordon, C. J., & Overton, J. M. (2014) · Physiology · doi:10.1152/physiol.00029.2014 · Cited by 177
“The primary site of nonshivering thermogenesis in rodents exposed to cold is BAT, and BAT stores increase when a rodent is exposed to cold (12).”
The role of stearoyl‐CoA desaturase in obesity, insulin resistance, and inflammation
Sampath, H., & Ntambi, J. M. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2011.06303.x · Cited by 164
Unstressing intemperate models: how cold stress undermines mouse modeling
Karp, C. L. (2012) · The Journal of Experimental Medicine · doi:10.1084/jem.20120988 · Cited by 161
“…areas with warmer annual ambient temperatures correlated with worse CF lung disease in four independent cohorts of patients on two continents (Collaco et al., 2011), underscoring the possibility that cold stress–driven inhibition of myeloid cell reactivity may play a major role in…”
Backgroundde Azúa, I. R., Mancini, G., Srivastava, R. K., Rey, A. A., Cardinal, P., Tedesco, L., Zingaretti, C. M., Sassmann, A., Quarta, C., Schwitter, C., et al. (2017) · Journal of Clinical Investigation · doi:10.1172/jci83626 · Cited by 168
“WAT is also innervated, although to a lesser degree, suggesting that alternative pathways participate in the regulation of Ucp1 expression in WAT.”
ResultInfluentialEng, J. W. ‐., Reed, C. B., Kokolus, K. M., Pitoniak, R., Utley, A. T., Bucsek, M. J., Ma, W. W., Repasky, E. A., & Hylander, B. L. (2015) · Nature Communications · doi:10.1038/ncomms7426 · Cited by 157
Yu, S., Qualls‐Creekmore, E., Rezai-Zadeh, K. P., Jiang, Y., Berthoud, H., Morrison, C. D., Derbenev, A. V., Zsombok, A., & Münzberg, H. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0213-16.2016 · Cited by 160
“We further speculate that LepRb POA neurons also modulate basal metabolic rate because pharmacogenetic activation of LepRb POA neurons still caused a significant decrease in energy expenditure at thermoneutrality (30°C), at which adaptive thermogenesis does not contribute to energy expenditure (Cannon and Nedergaard,…”
BackgroundInfluentialEffects of Rodent Thermoregulation on Animal Models in the Research Environment
Hankenson, F. C., Marx, J. O., Gordon, C. J., & David, J. M. (2018) · Comparative Medicine · doi:10.30802/aalas-cm-18-000049 · Cited by 171
UCP1-independent thermogenesis
Roesler, A. A., & Kazak, L. (2020) · Biochemical Journal · doi:10.1042/bcj20190463 · Cited by 163
Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism
Valencak, T. G., Osterrieder, A., & Schulz, T. J. (2017) · Redox Biology · doi:10.1016/j.redox.2017.04.012 · Cited by 156
Dyar, K. A., Hubert, M. J., Mir, A. A., Ciciliot, S., Lutter, D., Greulich, F., Quagliarini, F., Kleinert, M., Fischer, K., Eichmann, T. O., et al. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005886 · Cited by 159
Analysis of energy metabolism in humans: A review of methodologies
Lam, Y. Y., & Ravussin, É. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.09.005 · Cited by 175
“When mammals are exposed to temperatures outside their thermoneutral zone (a range of ambient temperatures within which basal metabolism is sufficient to maintain body temperature), thermoregulation mechanisms kick in to defend the body temperature set-point, and, subsequently, metabolic rate will increase [57].”
BackgroundTian, X. Y., Ganeshan, K., Hong, C., Nguyen, K. D., Qiu, Y., Kim, J., Tangirala, R. K., Tontonoz, P., & Chawla, A. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.10.003 · Cited by 155
“A large number of preclinical studies with genetically modified mice have linked adipose tissue inflammation to the develop- 4 Cell Metabolism 23, 1–14, January 12, 2016 ª2016 Elsevier Inc. ment of obesity-associated insulin resistance (Mathis, 2013; Odegaard and Chawla, 2013a; Osborn andOlefsky, 2012).”
BackgroundInfluentialBakker, L. E. H., Boon, M. R., van der Linden, R. A. D., Arias‐Bouda, L. M. P., van Klinken, J. B., Smit, F., Verberne, H. J., Jukema, J. W., Tamsma, J. T., Havekes, L. M., et al. (2013) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(13)70156-6 · Cited by 155
Leptin Raises Defended Body Temperature without Activating Thermogenesis
Fischer, A. W., Hoefig, C. S., Abreu-Vieira, G., de Jong, J. M. A., Petrovič, N., Mittag, J., Cannon, B., & Nedergaard, J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.01.041 · Cited by 151
Self-citationUrolithin A exerts antiobesity effects through enhancing adipose tissue thermogenesis in mice
Xia, B., Shi, X., Xie, B., Zhu, M., Chen, Y., Chu, X. Y., Cai, G. H., Liu, M., Yang, S. Z., Mitchell, G. A., et al. (2020) · PLoS Biology · doi:10.1371/journal.pbio.3000688 · Cited by 156
“Louis, MO, USA) stimulation at 4 ̊C and thermoneutrality (30 ̊C) as described [82].”
MethodLi, G., Xie, C., Lu, S., Nichols, R. G., Tian, Y., Li, L., Patel, D., Ma, Y., Brocker, C. N., Yan, T., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.007 · Cited by 144
“Emerging evidence suggests that non-shivering thermogenesis can re-establish energy balance and therefore counter the effects of elevated energy intake (Cannon and Nedergaard, 2011).”
Cold-activated brown adipose tissue in human adults: methodological issues
van der Lans, A. A. J. J., Wierts, R., Vosselman, M. J., Schrauwen, P., Brans, B. T., & Lichtenbelt, W. D. V. M. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00021.2014 · Cited by 155
Chronic and acute effects of stress on energy balance: are there appropriate animal models?
Harris, R. B. S. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00361.2014 · Cited by 145
“Rodents are usually housed below thermoneutrality and have the opportunity to develop significant brown fat depots (40).”
BackgroundIntracellular thermometry with fluorescent sensors for thermal biology
Okabe, K., Sakaguchi, R., Shi, B., & Kiyonaka, S. (2018) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-018-2113-4 · Cited by 140
“However, whether muscles act as heatgenerating organs remains controversial [8].”
BackgroundGoldgof, M., Xiao, C., Chanturiya, T., Jou, W., Gavrilova, O., & Reitman, M. L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.568204 · Cited by 138
“7 The theoretical implications of the mouse/human differences in thermal biology for drug development have been noted (46-48), but we are unaware of pharmacotherapy studies actually evaluating this theory.”
Backgroundde Jong, J. M. A., Sun, W., Pires, N. D., Frontini, A., Balaz, M., Jespersen, N. Z., Feizi, A., Petrovic, K., Fischer, A. W., Bokhari, M. H., et al. (2019) · Nature Metabolism · doi:10.1038/s42255-019-0101-4 · Cited by 137
Self-citationLiu, T.-F., Tang, J.-J., Li, P.-S., Shen, Y., Li, J.-G., Miao, H.-H., Li, B.-L., & Song, B.-L. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.06.014 · Cited by 127
Srivastava, S., Kashiwaya, Y., King, M. T., Baxa, U., Tam, J., Niu, G., Chen, X. S., Clarke, K., & Veech, R. L. (2012) · The FASEB Journal · doi:10.1096/fj.11-200410 · Cited by 133
“Data are presented on a per mouse basis and are not normalized to body weight (31, 32).”
BackgroundThermoneutrality decreases thermogenic program and promotes adiposity in high-fat diet-fed mice
Cui, X., Nguyen, N. L. T., Zarebidaki, E., Cao, Q., Li, F., Zha, L., Bartness, T. J., Shi, H., & Xue, B. (2016) · Physiological Reports · doi:10.14814/phy2.12799 · Cited by 135
Estrogen-sensitive medial preoptic area neurons coordinate torpor in mice
Zhang, Z., Reis, F. M., He, Y., Park, J. W., DiVittorio, J. R., Sivakumar, N., van Veen, J. E., Maesta‐Pereira, S., Shum, M., Nichols, I., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-20050-1 · Cited by 144
Dermal white adipose tissue: a new component of the thermogenic response
Alexander, C. M., Kasza, I., Yen, C.-L., Reeder, S. B., Hernando, D., Gallo, R. L., Jahoda, C. A. B., Horsley, V., & MacDougald, O. A. (2015) · Journal of Lipid Research · doi:10.1194/jlr.r062893 · Cited by 140
Lai, M.-C., Chandrasekera, P. C., & Barnard, N. D. (2014) · Nutrition and Diabetes · doi:10.1038/nutd.2014.30 · Cited by 133
Sakaguchi, M., Fujisaka, S., Cai, W., Winnay, J. N., Konishi, M., O'Neill, B. T., Li, M., García-Martín, R., Takahashi, H., Hu, J., et al. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2016.12.008 · Cited by 125
“To examine response to adrenergic stimulation, mice were injected intraperitoneally with a b3-adrenergic receptor-specific agonist CL-316,243 1 mg/kg (Cannon and Nedergaard, 2011).”
MethodXiao, C., Goldgof, M., Gavrilova, O., & Reitman, M. L. (2015) · Obesity · doi:10.1002/oby.21124 · Cited by 126
“thermoneutrality for mice (3,4); cold-induced thermogenesis for sin-”
Reber, J., Willershäuser, M., Karlas, A., Paul-Yuan, K., Diot, G., Franz, D., Fromme, T., Ovsepian, S. V., Bézière, N., Goun, E. A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.02.002 · Cited by 129
Hao, Q., Yadav, R., Basse, A. L., Petersen, S., Sonne, S. B., Rasmussen, S., Zhu, Q., Lu, Z., Wang, J., Audouze, K., et al. (2014) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00277.2014 · Cited by 127
“treatment with a β-adrenergic receptor agonist and selective sympathetic stimulation in iBAT during 405 cold exposure (4).”
MethodZuriaga, M. A., Fuster, J. J., Gokce, N., & Walsh, K. (2017) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2017.00027 · Cited by 122
“Humans have replaced the endogenous thermoregulatory mechanisms with the donning of clothing and macro-environmental manipulations (39).”
Central control of thermogenesis
Clapham, J. C. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.10.014 · Cited by 128
“…methods there are a number of potential pitfalls that should be heeded in both how data from the measurement of gases is transformed and in how the experiments are conducted in the live-phase, at the animals thermoneutral temperature for example (Arch et al., 2006; Cannon and Nedergaard, 2011).”
The role of somatosensory innervation of adipose tissues
Wang, Y., Leung, V. H., Zhang, Y., Nudell, V., Loud, M. C., Servin‐Vences, M. R., Yang, D. U., Wang, K., Moya-Garzón, M. D., Li, V. L., et al. (2022) · Nature · doi:10.1038/s41586-022-05137-7 · Cited by 126
Perinatal Licensing of Thermogenesis by IL-33 and ST2
Odegaard, J. I., Lee, M.-W., Sogawa, Y., Bertholet, A. M., Locksley, R. M., Weinberg, D. E., Kirichok, Y., Deo, R. C., & Chawla, A. (2016) · Cell · doi:10.1016/j.cell.2016.06.040 · Cited by 119
“In mammals, two types of programs support thermal homeostasis in cold environments: heat conservation and heat generation (Cannon and Nedergaard, 2011; Lowell and Spiegelman, 2000).”
InfluentialLight modulates glucose metabolism by a retina-hypothalamus-brown adipose tissue axis
Meng, J.-J., Shen, J., Li, G., Ouyang, C., Hu, J., Li, Z., Zhao, H., Shi, Y., Zhang, M., Liu, R., et al. (2023) · Cell · doi:10.1016/j.cell.2022.12.024 · Cited by 122
Brown Adipose Tissue and Its Role in Insulin and Glucose Homeostasis
Maliszewska, K., & Kretowski, A. J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22041530 · Cited by 124
“A second description of total daily energy expenditure is the use of obligatory and facultative thermogenesis [34].”
BackgroundBrite/beige fat and UCP1 — is it thermogenesis?
Keipert, S., & Jastroch, M. (2014) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2014.02.008 · Cited by 120
“However, counter arguments may be posited as body temperature is also maintained without functional BAT [21] and as the adaptive part of nonshivering thermogenesis requires comparison to and measurement in thermoneutrality [30].”
BackgroundCold-induced thermogenesis in humans
Brychta, R. J., & Chen, K. Y. (2016) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2016.223 · Cited by 122
Evolved Mechanisms of Aerobic Performance and Hypoxia Resistance in High-Altitude Natives
McClelland, G. B., & Scott, G. R. (2018) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021317-121527 · Cited by 113
“Abbreviations: ADP, adenosine 5′-diphosphate; BAT, brown adipose tissue; β-ox, β-oxidation; FAT/CD36, fatty acid translocase; GLUT, glucose transporter; HK, hexokinase; IMTG, intramuscular triglyceride; P, phosphorylated; PDH, pyruvate dehydrogenase; Pi, inorganic phosphate; TCA, tricarboxcylic acid; UCP-1, uncoupling…”
BackgroundInfluentialChen, K. Y., Brychta, R. J., Sater, Z. A., Cassimatis, T. M., Cero, C., Fletcher, L. A., Israni, N. S., Johnson, J. W., Lea, H. J., Linderman, J. D., et al. (2019) · Journal of Biological Chemistry · doi:10.1074/jbc.rev119.007363 · Cited by 121
“The detailed relationship between EE and environmental temperature is largely based on classical animal studies by Kleiber (6) and Scholander et al. (7), and more recently by Cannon, Nedergaard, and co-workers (5, 8) and Abreu-Vieira et al. (9).”
BackgroundInfluential
Metadata
- Authors
- Cannon, B., & Nedergaard, J.
- Affiliations
- Stockholm University (SE)
- Corresponding author
- Cannon, Barbara
- Venue
- Journal of Experimental Biology
- Publisher
- The Company of Biologists
- Published
- 2011-01-15
- Volume
- 214
- Issue
- 2
- Pages
- 242-253
- ISSN
- 0022-0949 (ISSN-L)
- 1477-9145
- OpenAlex
- W2148400263
- Cited by
- 677
- References
- 99
- Citations by year
- 2026: 20 · 2025: 31 · 2024: 32 · 2023: 45 · 2022: 42 · 2021: 55 · 2020: 53 · 2019: 42 · 2018: 69 · 2017: 48 · 2016: 47 · 2015: 42 · 2014: 48 · 2013: 48 · 2012: 41
- FWCI
- 3.31
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- other-oa
- Locations
- Journal of Experimental Biology (publishedVersion, other-oa)
- PubMed (publishedVersion)
- RVC Research Online (Royal Veterinary College) (submittedVersion, cc-by)
- Funders
- Vetenskapsrådet
- Topics
- Health Sciences › Medicine › Physiology (medical) › Adipose Tissue and Metabolism
- Physical Sciences › Environmental Science › Ecology › Physiological and biochemical adaptations
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Keywords
- non-shivering thermogenesis, brown adipose tissue, thermoneutrality, ambient temperature, metabolic rate measurement, norepinephrine, shivering, diet-induced thermogenesis, obesity, energy balance, mice, fur insulation
- MeSH terms
- Acclimatization, Animals, Adipose Tissue, Brown, Cold Temperature, Humans, Norepinephrine, Thermogenesis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
