A basic property of endothermic thermoregulation is the ability to generate heat by increasing metabolism in response to cold ambient temperatures to maintain a stable core body temperature. This process, known as cold-induced thermogenesis (CIT), has been measured in humans as early as 1780 by Antoine Lavoisier, but has found renewed interest because of the recent 'rediscovery' of thermogenic, cold-activated brown adipose tissue (BAT) in adult humans. In this review, we summarize some of the key findings of the work involving CIT over the past two centuries and highlight some of the seminal studies focused on this topic. There has been a substantial range of variability in the reported CIT in these studies, from 0 to 280% above basal metabolism. We identify and discuss several potential sources of this variability, including both methodological (measurement device, cold exposure temperature and duration) and biological (age and body composition of subject population) discrepancies. These factors should be considered when measuring CIT going forward to better assess whether BAT or other thermogenic organs are viable targets to combat chronic positive energy balance based on their relative capacities to elevate human metabolism.
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Snitker S, Macdonald I, Ravussin E, Astrup A . The sympathetic nervous system and obesity: role in aetiology and treatment. Obes Rev 2000; 1: 5–15.
Abreu-Vieira G, Xiao C, Gavrilova O, Reitman ML . Integration of body temperature into the analysis of energy expenditure in the mouse. Mol Metab 2015; 4: 461–470.
Cannon B, Nedergaard J . Nonshivering thermogenesis and its adequate measurement in metabolic studies. J Exp Biol 2011; 214: 242–253.
Gordon CJ . Thermal physiology of laboratory mice: defining thermoneutrality. J Therm Biol 2012; 37: 654–685.
Kleiber M . The Fire of Life: An Introduction to Animal Energetics. Wiley: New York, NY, USA, 1961, pp 105–171.
Fristoe TS, Burger JR, Balk MA, Khaliq I, Hof C, Brown JH . Metabolic heat production and thermal conductance are mass-independent adaptations to thermal environment in birds and mammals. Proc Natl Acad Sci USA 2015; 112: 15934–15939.
Fischer AW, Csikasz RI, von Essen G, Cannon B, Nedergaard J . No insulating effect of obesity. Am J Physiol Endocrinol Metab 2016; 311: E202–E213.
Scholander PF, Hock R, Walters V, Johnson F, Irving L . Heat regulation in some arctic and tropical mammals and birds. Biol Bull 1950; 99: 237–258.
Lusk G . The Elements of the Science of Nutrition, 4th edn Academic Press: New York, NY, USA, 1976, pp 18–19.
Voit C . Ueber die Wirkung der Temperatur der umgebenden Luft auf die Zersetsung im Organismus der Warmblüter. Z Biol 1878; 14: 57–160.
Swift RW . The effects of low environmental temperature upon metabolism II. The influence of shivering, subcutaneous fat, and skin temperature on heat production. J Nutr 1932; 5: 227–249.
Swift RW . The effects of low environmental temperature upon metabolism I. Technic and respiratory quotient. J Nutr 1932; 5: 213–225.
Hardy JD, Dubois EF . Regulation of heat loss from the human body. Proc Natl Acad Sci USA 1937; 23: 624–631.
Winslow CEA, Herrington LP, Gagge AP . Physiological reactions of the human body to varying environmental temperatures. Am J Physiol 1937; 120: 1–22.
Dubois EF, Ebaugh FG Jr, Hardy JD . Basal heat production and elimination of thirteen normal women at temperatures from 22 degrees C. to 35 degrees C. J Nutr 1952; 48: 257–293.
Buskirk ER, Thompson RH, Moore R, Whedon GD . Human energy expenditure studies in the National Institute of Arthritis and Metabolic Diseases metabolic chamber.1. Interaction of cold environment and spcific dynamic effect. 2. Sleep. Am J Clin Nutr 1960; 8: 602–613.
Donahoo WT, Levine JA, Melanson EL . Variability in energy expenditure and its components. Curr Opin Clin Nutr Metab Care 2004; 7: 599–605.
Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA et al. Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab 2016; 24: 210–222.
Craig AB Jr, Dvorak M . Thermal regulation during water immersion. J Appl Physiol 1966; 21: 1577–1585.
Young A, Sawka M, Pandolf K . The Physiology of Cold Exposure. In: Marriot BM, Carlson SJ (eds). Nutritional Needs in Cold and High-Altitude Environments: Applications for Military Personnel in Field Operations, Chapter 7. National Academy Press: Washington, DC, USA, 1996, pp 127–148.
Cannon P, Keatinge WR . The metabolic rate and heat loss of fat and thin men in heat balance in cold and warm water. J Physiol 1960; 154: 329–344.
Young AJ, Castellani JW, O'Brien C, Shippee RL, Tikuisis P, Meyer LG et al. Exertional fatigue, sleep loss, and negative energy balance increase susceptibility to hypothermia. J Appl Physiol (1985) 1998; 85: 1210–1217.
Haman F . Shivering in the cold: from mechanisms of fuel selection to survival. J Appl Physiol (1985) 2006; 100: 1702–1708.
Kilgour RD, Williams PA . Effects of diabetes and food deprivation on shivering activity during progressive hypothermia in the rat. Comp Biochem Physiol A 1996; 114: 159–165.
Blondin DP, Labbé SM, Tingelstad HC, Noll C, Kunach M, Phoenix S et al. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab 2014; 99: E438–E446.
Tikuisis P, Bell DG, Jacobs I . Shivering onset, metabolic response, and convective heat transfer during cold air exposure. J Appl Physiol (1985) 1991; 70: 1996–2002.
Blaxter K . Energy Metabolism in Animals and Man, vol. 110. Cambridge University Press: Cambridge, MA, USA, 1989.
Warwick PM, Busby R . Influence of mild cold on 24 h energy expenditure in 'normally' clothed adults. Br J Nutr 1990; 63: 481–488.
Claessens-van Ooijen AM, Westerterp KR, Wouters L, Schoffelen PF, van Steenhoven AA, van Marken Lichtenbelt WD et al. Heat production and body temperature during cooling and rewarming in overweight and lean men. Obesity (Silver Spring) 2006; 14: 1914–1920.
Wijers SL, Saris WH, van Marken Lichtenbelt WD . Cold-induced adaptive thermogenesis in lean and obese. Obesity (Silver Spring) 2010; 18: 1092–1099.
van Marken Lichtenbelt WD, Westerterp-Plantenga MS, van Hoydonck P . Individual variation in the relation between body temperature and energy expenditure in response to elevated ambient temperature. Physiol Behav 2001; 73: 235–242.
Davis TR . Chamber cold acclimatization in man. J Appl Physiol 1961; 16: 1011–1015.
Irving L . Human adaptation to cold. Nature 1960; 185: 572–574.
Scholander PF, Hammel HT, Andersen KL, Loyning Y . Metabolic acclimation to cold in man. J Appl Physiol 1958; 12: 1–8.
Scholander PF, Hammel HT, Hart JS, Lemessurier DH, Steen J . Cold adaptation in Australian aborigines. J Appl Physiol 1958; 13: 211–218.
Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med 2009; 360: 1509–1517.
Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 2009; 58: 1526–1531.
van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med 2009; 360: 1500–1508.
Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T et al. Functional brown adipose tissue in healthy adults. N Engl J Med 2009; 360: 1518–1525.
Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab 2013; 98: E1218–E1223.
Ouellet V, Labbé SM, Blondin DP, Phoenix S, Guérin B, Haman F et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 2012; 122: 545–552.
Blondin DP, Labbé SM, Noll C, Kunach M, Phoenix S, Guérin B et al. Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes. Diabetes 2015; 64: 2388–2397.
Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J, Granneman JG et al. 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med 2013; 54: 523–531.
Dulloo AG . Translational issues in targeting brown adipose tissue thermogenesis for human obesity management. Ann NY Acad Sci 2013; 1302: 1–10.
Hanssen MJ, Hoeks J, Brans B, van der Lans AA, Schaart G, van den Driessche JJ et al. Short-term cold acclimation improves insulin sensitivity in patients with type 2 diabetes mellitus. Nat Med 2015; 21: 863–865.
Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, Schaart G et al. Short-term cold acclimation recruits brown adipose tissue in obese humans. Diabetes 2016; 65: 1179–1189.
Lee P, Smith S, Linderman J, Courville AB, Brychta RJ, Dieckmann W et al. Temperature-acclimated brown adipose tissue modulates insulin sensitivity in humans. Diabetes 2014; 63: 3686–3698.
van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ et al. Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest 2013; 123: 3395–3403.
Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y et al. Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 2013; 123: 3404–3408.
Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y et al. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity (Silver Spring) 2011; 19: 1755–1760.
Frank SM, Raja SN, Bulcao C, Goldstein DS . Age-related thermoregulatory differences during core cooling in humans. Am J Physiol 2000; 279: R349–R354.
Winslow CEA, Herrington LP, Gagge AP . The determination of radiation and convection exchanges by partitional calorimetry. Am J Physiol 1936; 116: 669–684.
Winslow CEA, Herrington LP, Gagge AP . A new method of partitional calorimetry. Am J Physiol 1936; 116: 641–655.
Dauncey MJ . Influence of mild cold on 24 h energy expenditure, resting metabolism and diet-induced thermogenesis. Br J Nutr 1981; 45: 257–267.
van Marken Lichtenbelt WD, Schrauwen P, van De Kerckhove S, Westerterp-Plantenga MS . Individual variation in body temperature and energy expenditure in response to mild cold. Am J Physiol Endocrinol Metab 2002; 282: E1077–E1083.
Westerterp-Plantenga MS, van Marken Lichtenbelt WD, Strobbe H, Schrauwen P . Energy metabolism in humans at a lowered ambient temperature. Eur J Clin Nutr 2002; 56: 288–296.
Schrauwen P, Westerterp-Plantenga MS, Kornips E, Schaart G, van Marken Lichtenbelt WD . The effect of mild cold exposure on UCP3 mRNA expression and UCP3 protein content in humans. Int J Obes Relat Metab Disord 2002; 26: 450–457.
Westerterp-Plantenga MS, van Marken Lichtenbelt WD, Cilissen C, Top S . Energy metabolism in women during short exposure to the thermoneutral zone. Physiol Behav 2002; 75: 227–235.
Wijers SL, Saris WH, van Marken Lichtenbelt WD . Individual thermogenic responses to mild cold and overfeeding are closely related. J Clin Endocrinol Metab 2007; 92: 4299–4305.
Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt WD . Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis. PLoS One 2008; 3: e1777.
Celi FS, Brychta RJ, Linderman JD, Butler PW, Alberobello AT, Smith S et al. Minimal changes in environmental temperature result in a significant increase in energy expenditure and changes in the hormonal homeostasis in healthy adults. Eur J Endocrinol 2010; 163: 863–872.
Wijers SL, Schrauwen P, van Baak MA, Saris WH, van Marken Lichtenbelt WD . Beta-adrenergic receptor blockade does not inhibit cold-induced thermogenesis in humans: possible involvement of brown adipose tissue. J Clin Endocrinol Metab 2011; 96: E598–E605.
Rennie DW, Covino BG, Blair MR, Rodahl K . Physical regulation of temperature in Eskimos. J Appl Physiol 1962; 17: 326–332.
Vallerand AL, Savourey G, Bittel JH . Determination of heat debt in the cold: partitional calorimetry vs. conventional methods. J Appl Physiol (1985) 1992; 72: 1380–1385.
van Ooijen AM, van Marken Lichtenbelt WD, van Steenhoven AA, Westerterp KR . Seasonal changes in metabolic and temperature responses to cold air in humans. Physiol Behav 2004; 82: 545–553.
Vosselman MJ, van der Lans AA, Brans B, Wierts R, van Baak MA, Schrauwen P et al. Systemic beta-adrenergic stimulation of thermogenesis is not accompanied by brown adipose tissue activity in humans. Diabetes 2012; 61: 3106–3113.
Vosselman MJ, Brans B, van der Lans AA, Wierts R, van Baak MA, Mottaghy FM et al. Brown adipose tissue activity after a high-calorie meal in humans. Am J Clin Nutr 2013; 98: 57–64.
Vosselman MJ, Hoeks J, Brans B, Pallubinsky H, Nascimento EB, van der Lans AA et al. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int J Obes (Lond) 2015; 39: 1696–1702.
van der Lans AA, Vosselman MJ, Hanssen MJ, Brans B, van Marken Lichtenbelt WD . Supraclavicular skin temperature and BAT activity in lean healthy adults. J Physiol Sci 2016; 66: 77–83.
Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y et al. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring) 2011; 19: 13–16.
Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O et al. Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci USA 2012; 109: 10001–10005.
Cypess AM, Weiner LS, Roberts-Toler C, Franquet-Elia E, Kessler SH, Kahn PA et al. Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab 2015; 21: 33–38.
Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C et al. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 2014; 19: 302–309.
This work was funded by NIH Intramural research funding resources (NIDDK and Clinical Center).
The authors declare no conflict of interest.
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