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Brown adipose tissue: physiological function and evolutionary significance

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Abstract

In modern eutherian (placental) mammals, brown adipose tissue (BAT) evolved as a specialized thermogenic organ that is responsible for adaptive non-shivering thermogenesis (NST). For NST, energy metabolism of BAT mitochondria is increased by activation of uncoupling protein 1 (UCP1), which dissipates the proton motive force as heat. Despite the presence of UCP1 orthologues prior to the divergence of teleost fish and mammalian lineages, UCP1’s significance for thermogenic adipose tissue emerged at later evolutionary stages. Recent studies on the presence of BAT in metatherians (marsupials) and eutherians of the afrotherian clade provide novel insights into the evolution of adaptive NST in mammals. In particular studies on the ‘protoendothermic’ lesser hedgehog tenrec (Afrotheria) suggest an evolutionary scenario linking BAT to the onset of eutherian endothermy. Here, we review the physiological function and distribution of BAT in an evolutionary context by focusing on the latest research on phylogenetically distinct species.

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Abbreviations

BAT:

Brown adipose tissue

NST:

Non-shivering thermogenesis

UCP1:

Uncoupling protein 1

References

  • Adamsons K, Blumberg E, Joelsson I (1969) The effect of ambient temperature upon post-natal changes in oxygen consumption of the guinea-pig. J Physiol 202:261–269

    CAS  PubMed Central  PubMed  Google Scholar 

  • Amiel JJ, Shine R (2012) Hotter nests produce smarter young lizards. Biol Lett 8:372–374. doi:10.1098/rsbl.2011.1161

    PubMed Central  PubMed  Google Scholar 

  • Aquila H, Link TA, Klingenberg M (1985) The uncoupling protein from brown fat mitochondria is related to the mitochondrial ADP/ATP carrier. Analysis of sequence homologies and of folding of the protein in the membrane. EMBO J 4:2369–2376

    CAS  PubMed Central  PubMed  Google Scholar 

  • Avery R (1979) Lizards: a study of thermoregulation. In: Institute of Biology’s Studies in Biology, vol 109

  • Bakken G, Gates D (1975) Heat transfer analysis of animals: some implications for field ecology, physiology and evolution. In: Gates D, Schmerl R (eds) Perspectives in biophysical ecology. Springer, New York, pp 255–290

    Google Scholar 

  • Bakker RT (1971) Dinosaur physiology and the origin of mammals. Evolution 25:636–658. doi:10.2307/2406945

    Google Scholar 

  • Bal NC, Maurya SK, Sopariwala DH, Sahoo SK, Gupta SC, Shaikh SA (2012) Sarcolipin is a newly identified regulator of muscle-based thermogenesis in mammals. Nat Med 18:1575–1579. doi:10.1038/nm.2897

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bartness TJ, Vaughan CH, Song CK (2010) Sympathetic and sensory innervation of brown adipose tissue. Int J Obes 34:36–42. doi:10.1038/ijo.2010.182

    Google Scholar 

  • Bell K, Blomberg S, Schwarzkopf L (2013) Detrimental influence on performance of high temperature incubation in a tropical reptile: is cooler better in the tropics? Oecologia 171:83–91. doi:10.1007/s00442-012-2409-6

    PubMed  Google Scholar 

  • Bennett AF (1991) The evolution of activity capacity. J Exp Biol 160:1–23

    CAS  PubMed  Google Scholar 

  • Bennett AF, Ruben JA (1979) Endothermy and activity in vertebrates. Science 206:649–654

    CAS  PubMed  Google Scholar 

  • Berg F, Gustafson U, Andersson L (2006) The uncoupling protein 1 gene (UCP1) is disrupted in the pig lineage: a genetic explanation for poor thermoregulation in piglets. PLoS Genet 2:1178–1181. doi:10.1371/journal.pgen.0020129

    CAS  Google Scholar 

  • Bernson SM, Nicholls DG (1974) Acetate, a major end product of fatty-acid oxidation in hamster brown-adipose-tissue mitochondria. Eur J Biochem 47:517–525

    CAS  PubMed  Google Scholar 

  • Berthon D, Herpin P, Le Dividic J (1995) Shivering is the main thermogenic mechanism in cold-exposed newborn pigs. Proc Nutr Soc 54:87

    Google Scholar 

  • Bicudo JE, Bianco AC, Vianna CR (2002) Adaptive thermogenesis in hummingbirds. J Exp Biol 205:2267–2273

    PubMed  Google Scholar 

  • Block B (1991) Endothermy in fish: thermogenesis, ecology and evolution. In: Hochachka PW, Mommsen TP (eds) Biochemistry and molecular biology of fishes. Elsevier, New York, pp 269–311

    Google Scholar 

  • Böckler H, Steinlechner S, Heldmaier G (1982) Complete cold substitution of noradrenaline-induced thermogenesis in the Djungarian hamster, Phodopus sungorus. Experientia 38:261–262

    PubMed  Google Scholar 

  • Boss O, Samec S, Kühne F, Bijlenga P, Assimacopoulos-Jeannet F, Seydoux J, Giacobino JP, Muzzin P (1998) Uncoupling protein-3 expression in rodent skeletal muscle is modulated by food intake but not by changes in environmental temperature. J Biol Chem 273:5–8

    CAS  PubMed  Google Scholar 

  • Bouillaud F, Ricquier D, Thibault J, Weissenbach J (1985) Molecular approach to thermogenesis in brown adipose tissue: cDNA cloning of the mitochondrial uncoupling protein. Proc Natl Acad Sci USA 82:445–448

    CAS  PubMed Central  PubMed  Google Scholar 

  • Brück K, Wünnenberg B (1966) Influence of ambient temperature in the process of replacement of nonshivering by shivering thermogenesis during postnatal development. Fed Proc 25:1332–1337

    PubMed  Google Scholar 

  • Brück K, Wünnenberg W, Zeisberger E (1969) Comparison of cold-adaptive metabolic modifications in different species, with special reference to the miniature pig. Fed Proc 28:1035–1041

    PubMed  Google Scholar 

  • Buffenstein R (1996) Ecophysiological responses to a subterranean habitat; a Bathyergid perspective. Mammalia 60:591–605

    Google Scholar 

  • Buffenstein R, Yahav S (1991) Is the naked mole rat Heterocephalus glaber an endothermic yet poikilothermic mammal? J Therm Biol 16:227–232

    Google Scholar 

  • Cambon B, Reyne Y, Nouguès J (1998) In vitro induction of UCP1 mRNA in preadipocytes from rabbit considered as a model of large mammals brown adipose tissue development: importance of PPARgamma agonists for cells isolated in the postnatal period. Mol Cell Endocrinol 146:49–58

    CAS  PubMed  Google Scholar 

  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359. doi:10.1152/physrev.00015.2003

    CAS  PubMed  Google Scholar 

  • Cannon B, Vogel G (1977) The mitochondrial ATPase of brown adipose tissue. Purification and comparison with the mitochondrial ATPase from beef heart. FEBS Lett 76:284–289

    CAS  PubMed  Google Scholar 

  • Cannon B, Romert L, Sundin U, Barnard T (1977) Morphology and biochemical properties of perirenal adipose tissue from lamb (Ovis aries). A comparison with brown adipose tissue. Comp Biochem Physiol B 56:87–99

    CAS  PubMed  Google Scholar 

  • Carrière A, Jeanson Y, Berger-Müller S, André M, Chenouard V, Arnaud E, Barreau C, Walther R, Galinier A, Wdziekonski B, Villageois P, Louche K, Collas P, Moro C, Dani C, Villarroya F, Casteilla L (2014) Browning of white adipose cells by intermediate metabolites: an adaptive mechanism to alleviate redox pressure. Diabetes. doi:10.2337/db13-1885

    PubMed  Google Scholar 

  • Carroll AM, Haines LR, Pearson TW, Fallon PG, Walsh CM, Brennan CM, Breen EP, Porter RK (2005) Identification of a functioning mitochondrial uncoupling protein 1 in thymus. J Biol Chem 280:15534–15543. doi:10.1074/jbc.M413315200

    CAS  PubMed  Google Scholar 

  • Casteilla L, Champigny O, Bouillaud F, Robelin J, Ricquier D (1989) Sequential changes in the expression of mitochondrial protein mRNA during the development of brown adipose tissue in bovine and ovine species. Sudden occurrence of uncoupling protein mRNA during embryogenesis and its disappearance after birth. Biochem J 257:665–671

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chen JF, Zhong WQ, Wang DH (2012) Seasonal changes in body mass, energy intake and thermogenesis in Maximowiczi’s voles (Microtus maximowiczii) from the inner Mongolian grassland. J Comp Physiol B 182:275–285. doi:10.1007/s00360-011-0608-9

    PubMed  Google Scholar 

  • Chi QS, Wang DH (2011) Thermal physiology and energetics in male desert hamsters (Phodopus roborovskii) during cold acclimation. J Comp Physiol B 181:91–103. doi:10.1007/s00360-010-0506-6

    PubMed  Google Scholar 

  • Clarke KJ, Porter RK (2012) Uncoupling protein 1 dependent reactive oxygen species production by thymus mitochondria. Int J Biochem Cell Biol 45:81–89. doi:10.1016/j.biocel.2012.09.023

    PubMed  Google Scholar 

  • Clarke DN, Zani PA (2012) Effects of night-time warming on temperate ectotherm reproduction: potential fitness benefits of climate change for side-blotched lizards. J Exp Biol 215:1117–11127. doi:10.1242/jeb065359

    PubMed  Google Scholar 

  • Clarke L, Buss DS, Juniper DT, Lomax MA, Symonds ME (1997a) Adipose tissue development during early postnatal life in ewe-reared lambs. Exp Physiol 82:1015–1027

    CAS  PubMed  Google Scholar 

  • Clarke L, Heasman L, Firth K, Symonds ME (1997b) Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs. Am J Physiol 272:1931–1939

    Google Scholar 

  • Clements F, Hope P, Daniels C, Chapman I, Wittert G (1998) Thermogenesis in the marsupial Sminthopsis crassicaudata: effect of catecholamines and diet. Aust J Zool 46:381–390

    Google Scholar 

  • Coulter AA, Bearden CM, Liu X, Koza RA, Kozak LP (2003) Dietary fat interacts with QTLs controlling induction of Pgc-1α and Ucp1 during conversion of white to brown fat. Physiol Genomics 14:139–147

    CAS  PubMed  Google Scholar 

  • Crompton AW, Taylor CR, Jagger JA (1978) Evolution of homeothermy in mammals. Nature 272:333–336

    CAS  PubMed  Google Scholar 

  • Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360:1509–1517. doi:10.1056/NEJMoa0810780

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, Huang TL, Roberts-Toler C, Weiner LS, Sze C, Chacko AT, Deschamps LN, Herder LM, Truchan N, Glasgow AL, Holman AR, Gavrila A, Hasselgren PO, Mori MA, Molla M, Tseng YH (2013) Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med 19:635–669. doi:10.1038/nm.3112

    CAS  PubMed Central  PubMed  Google Scholar 

  • Cypess AM, Haft CR, Laughlin MR, Hu HH (2014) Brown fat in humans: consensus points and experimental guidelines. Cell Metab 20:408–415. doi:10.1016/j.cmet.2014.07.025

    CAS  PubMed  Google Scholar 

  • Darby CJ, Clarke L, Lomax MA, Symonds ME (1996) Brown adipose tissue and liver development during early postnatal life in hand-reared and ewe-reared lambs. Reprod Fertil Dev 8:137–145

    CAS  PubMed  Google Scholar 

  • Dauncey MJ, Wooding FB, Ingram DL (1981) Evidence for the presence of brown adipose tissue in the pig. Res Vet Sci 31:76–81

    CAS  PubMed  Google Scholar 

  • Dawson TJ, Olson JM (1988) Thermogenic capabilities of the opossum Monodelphis domestica when warm and cold acclimated: similarities between American and Australian marsupials. Comp Biochem Physiol A Comp Physiol 89:85–91

    CAS  PubMed  Google Scholar 

  • Divakaruni AS, Brand MD (2011) The regulation and physiology of mitochondrial proton leak. Physiology 26:192–205. doi:10.1152/physiol.00046.2010

    CAS  PubMed  Google Scholar 

  • Dlasková A, Clarke KJ, Porter RK (2010) The role of UCP 1 in production of reactive oxygen species by mitochondria isolated from brown adipose tissue. Biochim Biophys Acta 1797:1470–1476. doi:10.1016/j.bbabio.2010.04.008

    PubMed  Google Scholar 

  • Downs CT, Perrin MR (1991) Physiological adjustments to low temperatures of four Gerbillurus species. J Therm Biol 16:25–29. doi:10.1016/0306-4565(91)90047-6

    Google Scholar 

  • Edson JL, Hull D, Elphick MC (1981) The development of cold-induced thermogenesis in hamsters. J Dev Physiol 3:387–396

    CAS  PubMed  Google Scholar 

  • Else PL, Hulbert AJ (1981) Comparison of the “mammal machine” and the “reptile machine”: energy production. Am J Physiol 240:3–9

    Google Scholar 

  • Enerbäck S, Jacobsson A, Simpson EM, Guerra C, Yamashita H, Harper ME, Kozak LP (1997) Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387:90–94. doi:10.1038/387090a0

    PubMed  Google Scholar 

  • Ewing LL, Schanbacher LM (1970) Early effects of experimental cryptorchidism on the activity of selected enzymes in rat testes. Endocrinology 87:129–134. doi:10.1210/endo-87-1-129

    CAS  PubMed  Google Scholar 

  • Farmer C (2000) Parental care: the key to understanding endothermy and other convergent features in birds and mammals. Am Nat 155:326–334. doi:10.1086/303323

    PubMed  Google Scholar 

  • Fedorenko A, Lishko PV, Kirichok Y (2012) Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151:400–413. doi:10.1016/j.cell.2012.09.010

    CAS  PubMed Central  PubMed  Google Scholar 

  • Feist DD, Feist CF (1986) Effects of cold, short day and melatonin on thermogenesis, body weight and reproductive organs in Alaskan red-backed voles. J Comp Physiol B 156:741–746

    CAS  PubMed  Google Scholar 

  • Feist DD, Rosenmann M (1975) Seasonal sympatho-adrenal and metabolic responses to cold in the Alaskan snowshoe hare (Lepus americanus macfarlani). Comp Biochem Physiol A Comp Physiol 51:449–455

    CAS  PubMed  Google Scholar 

  • Fleury C, Neverova M, Collins S, Raimbault S, Champigny O, Levi-Meyrueis C, Bouillaud F, Seldin MF, Surwit RS, Ricquier D, Warden CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nat Genet 15:269–272. doi:10.1038/ng0397-269

    CAS  PubMed  Google Scholar 

  • Foster DO (1984) Quantitative contribution of brown adipose tissue thermogenesis to overall metabolism. Can J Biochem Cell Biol 62:618–622

    CAS  PubMed  Google Scholar 

  • Geiser F (2008) Ontogeny and phylogeny of endothermy and torpor in mammals and birds. Comp Biochem Physiol A Mol Integr Physiol 150:176–180. doi:10.1016/j.cbpa.2007.02.041

    PubMed  Google Scholar 

  • Gemmell RT, Bell AW, Alexander G (1972) Morphology of adipose cells in lambs at birth and during subsequent transition of brown to white adipose tissue in cold and in warm conditions. Am J Anat 133:143–163. doi:10.1002/aja.1001330203

    CAS  PubMed  Google Scholar 

  • Génin F, Nibbelink M, Galand M, Perret M, Ambid L (2003) Brown fat and nonshivering thermogenesis in the gray mouse lemur (Microcebus murinus). Am J Physiol Regul Integr Comp Physiol 284:811–818. doi:10.1152/ajpregu.00525.2002

    Google Scholar 

  • Gesner C (1551) Conradi Gesneri medici Tigurini Historiae Animalium: Lib 1—De Quadrupedibus Viviparis (Zürich), 842

  • Gettinger RD, Ralph CL (1985) Thermoregulatory responses to photoperiod by kangaroo rats (Dipodomys ordii): influence of night lighting on nonshivering thermogenesis and resting metabolism. J Exp Zool 234:335–340. doi:10.1002/jez.1402340302

    CAS  PubMed  Google Scholar 

  • Gimeno RE, Dembski M, Weng X, Deng N, Shyjan AW, Gimeno CJ, Iris F, Ellis SJ, Woolf EA, Tartaglia LA (1997) Cloning and characterization of an uncoupling protein homolog: a potential molecular mediator of human thermogenesis. Diabetes 46:900–906

    CAS  PubMed  Google Scholar 

  • Giralt M, Martin I, Iglesias R, Viñas O, Villarroya F, Mampel T (1990) Ontogeny and perinatal modulation of gene expression in rat brown adipose tissue. Unaltered iodothyronine 5′-deiodinase activity is necessary for the response to environmental temperature at birth. Eur J Biochem 193:297–302

    CAS  PubMed  Google Scholar 

  • Golozoubova V, Hohtola E, Matthias A, Jacobsson A, Cannon B, Nedergaard J (2001) Only UCP1 can mediate adaptive nonshivering thermogenesis in the cold. FASEB J 15:2048–2050. doi:10.1096/fj.00-0536fje

    CAS  PubMed  Google Scholar 

  • Grigg GC, Beard LA, Augee ML (2004) The evolution of endothermy and its diversity in mammals and birds. Physiol Biochem Zool 77:982–997. doi:10.1086/425188

    PubMed  Google Scholar 

  • Guerra C, Koza RA, Yamashita H, Wals K, Kozak LP (1998) Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest 102:412–420

    CAS  PubMed Central  PubMed  Google Scholar 

  • Gutowski JP, Wojciechowski MS, Jefimow M (2011) Diet affects resting, but not basal metabolic rate of normothermic Siberian hamsters acclimated to winter. Comp Biochem Physiol A Mol Integr Physiol 160:516–523. doi:10.1016/j.cbpa.2011.08.012

    CAS  PubMed  Google Scholar 

  • Haim A (1981) Heat production and dissipation in a South african diurnal murid Lemniscomys griselda. South African J Zool 16:67–70

    Google Scholar 

  • Haim A (1984) Adaptive variations in heat production within Gerbils (genus Gerbillus) from different habitats. Oecologia 61:49–52. doi:10.1007/BF00379087

    Google Scholar 

  • Haim A (1987) Thermoregulation and metabolism of Wagner’s Gerbil (Gerbillus dasyurus): a rock dwelling rodent adapted to arid and mesic environments. J Therm Biol 12:45–48. doi:10.1016/0306-4565(87)90022-2

    Google Scholar 

  • Haim A (1996) Food and energy intake, non-shivering thermogenesis and daily rhythm of body temperature in the bushy-tailed gerbil Sekeetamys calurus: the role of photoperiod manipulations. J Therm Biol 21:37–42. doi:10.1016/0306-4565(96)81275-7

    Google Scholar 

  • Haim A, Fairall N (1986) Physiological adaptations to the subterranean environment by the mole rat Cryptomys hottentotus. Cimbebasia Ser 8A:49–53

  • Haim A, Fairall N (1987) Bioenergetics of an herbivorous rodent Otomys irroratus. Physiol Zool 60:305–309. doi:10.2307/30162283

    Google Scholar 

  • Haim A, Fourie F (1980) Heat production in nocturnal (Praomys natalensis) and diurnal (Rhabdomys pumilio) South-African murids. South African J Zool 15:91–94

    Google Scholar 

  • Haim A, Harari J (1992) A comparative study of heat production and thermoregulation in two sympatric gerbils (Gerbillus gerbillus and G. pyramidum). Isr J Zool 38:363–372. doi:10.1080/00212210.1992.10688683

    Google Scholar 

  • Haim A, Izhaki I (1993) The ecological significance of resting metabolic rate and non-shivering thermogenesis for rodents. J Therm Biol 18:71–81. doi:10.1016/0306-4565(93)90019-P

    Google Scholar 

  • Haim A, Levi G (1990) Role of body temperature in seasonal acclimatization: photoperiod-induced rhythms and heat production in Meriones crassus. J Exp Zool 256:237–241. doi:10.1002/jez.1402560302

    Google Scholar 

  • Haim A, Yahav S (1982) Non-shivering thermogenesis in winter-acclimatized and in long-scotophase and cold-acclimated Apodemus mystacinus (Rodentia). J Therm Biol 7:193–195. doi:10.1016/0306-4565(82)90023-7

    Google Scholar 

  • Haim A, Heth G, Avnon Z, Nevo E (1984) Adaptive physiological variation in nonshivering thermogenesis and its significance in speciation. J Comp Physiol B 154:145–147. doi:10.1007/BF00684138

    Google Scholar 

  • Haim A, Skinner JD, Robinson TJ (1987) Bioenergetics, thermoregulation and urine analysis of squirrels of the genus Xerus from an arid environment. South Afr J Zool 22:45–49

    Google Scholar 

  • Haim A, Racey PA, Speakman JR, Skinner JD (1991) Seasonal acclimatization and thermoregulation in the pouched mouse Saccostomus campestris. J Therm Biol 16:13–17. doi:10.1016/0306-4565(91)90045-4

    Google Scholar 

  • Haim A, McDevitt R, Speakman J (1995) Daily variations in the response of wood mice Apodemus sylvaticus to noradrenaline. J Exp Biol 198:561–565

    CAS  PubMed  Google Scholar 

  • Haim A, Shabtay A, Arad Z (1998) Thermoregulatory responses of mesic and xeric rodent species to photoperiod manipulations. Comp Biochem Physiol A Mol Integr Physiol 120:187–191

    CAS  PubMed  Google Scholar 

  • Hammel HT (1955) Thermal properties of fur. Am J Physiol 182:369–376

    CAS  PubMed  Google Scholar 

  • Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252–1263. doi:10.1038/nm.3361

    CAS  PubMed  Google Scholar 

  • Hart JS (1952) Effects of temperature and work on metabolism, body temperature, and insulation: results with mice. Can J Zool 30:90–98. doi:10.1139/z52-007

    Google Scholar 

  • Hatai S (1902) On the presence in human embryos of an interscapular gland corresponding to the so-called hibernating gland of lower mammals. Ann Anat 21:369–373

    Google Scholar 

  • Hayes JP (1989) Altitudinal and seasonal effects on aerobic metabolism of deer mice. J Comp Physiol B 159:453–459

    CAS  PubMed  Google Scholar 

  • Hayes JP, Garland T (1995) The evolution of endothermy: testing the aerobic capacity model. Evolution 49:836–847. doi:10.2307/2410407

    Google Scholar 

  • Hayward JS (1968) The magnitude of noradrenaline-induced thermogenesis in the bat (Myotis lucifugus) and its relation to arousal from hibernation. Can J Physiol Pharmacol 46:713–718

    CAS  PubMed  Google Scholar 

  • Hayward JS, Lisson PA (1992) Evolution of brown fat: its absence in marsupials and monotremes. Can J Zool 70:171–179. doi:10.1139/z92-025

    Google Scholar 

  • Heath J (1968) Origins of thermoregulation. In: Drake E (ed) Evolution and environment. Yale University Press, New Haven, pp 259–278

    Google Scholar 

  • Heaton GM, Wagenvoord RJ, Kemp A, Nicholls DG (1978) Brown-adipose-tissue mitochondria: photoaffinity labelling of the regulatory site of energy dissipation. Eur J Biochem 82:515–521

    CAS  PubMed  Google Scholar 

  • Heinrich B (1977) Why have some animals evolved to regulate a high body temperature? Am Nat 111:623–640. doi:10.2307/2460321

    Google Scholar 

  • Heldmaier G (1970) Die Thermogenese der Mausohrfledermaus (Myotis myotis) beim Erwachen aus dem Winterschlaf. Z vergl Physiol 63:59–84

    Google Scholar 

  • Heldmaier G (1971) Zitterfreie Wärmebildung und Körpergröße bei Säugetieren. Z vergl Physiol 73:222–248

    Google Scholar 

  • Heldmaier G, Steinlechner S, Rafael J, Vsiansky P (1981) Photoperiodic control and effects of melatonin on nonshivering thermogenesis and brown adipose tissue. Science 212:917–919

    CAS  PubMed  Google Scholar 

  • Heldmaier G, Steinlechner S, Ruf T, Wiesinger H, Klingenspor M (1989) Photoperiod and thermoregulation in vertebrates: body temperature rhythms and thermogenic acclimation. J Biol Rhythms 4:251–265

    CAS  PubMed  Google Scholar 

  • Heldmaier G, Klaus S, Wiesinger H (1990) Seasonal adaptation of thermoregulatory heat production in small mammals. In: Voigt K, Bligh J (eds) Thermoreception and temperature regulation in mammals and birds. Springer, Berlin, pp 235–243

    Google Scholar 

  • Heldmaier G, Neuweiler G, Rössler W (2012) Vergleichende Tierphysiologie, 2nd edn. Springer Spektrum, Berlin

    Google Scholar 

  • Himms-Hagen J (1984) Thermogenesis in brown adipose tissue as an energy buffer. Implications for obesity. N Engl J Med 311:1549–1558. doi:10.1056/NEJM198412133112407

    CAS  PubMed  Google Scholar 

  • Hislop MS, Buffenstein R (1994) Noradrenaline induces nonshivering thermogenesis in both the naked mole-rat (Heterocephalus glaber) and the Damara mole-rat (Cryptomys damarensis) despite very different modes of thermoregulation. J Therm Biol 19:25–32. doi:10.1016/0306-4565(94)90006-X

    CAS  Google Scholar 

  • Hope PJ, Pyle D, Daniels CB, Chapman I, Horowitz M, Morley JE, Trayhurn P, Kumaratilake J, Wittert G (1997) Identification of brown fat and mechanisms for energy balance in the marsupial, Sminthopsis crassicaudata. Am J Physiol 273:161–167

    Google Scholar 

  • Houstĕk J, Janíková D, Bednár J, Kopecký J, Sebestián J, Soukup T (1990) Postnatal appearance of uncoupling protein and formation of thermogenic mitochondria in hamster brown adipose tissue. Biochim Biophys Acta 1015:441–449

    PubMed  Google Scholar 

  • Hsieh A, Carlson L (1957) Role of adrenaline and noradrenaline in chemical regulation of heat production. Am J Physiol 190:243–246

    CAS  PubMed  Google Scholar 

  • Hughes DA, Jastroch M, Stoneking M, Klingenspor M (2009) Molecular evolution of UCP1 and the evolutionary history of mammalian non-shivering thermogenesis. BMC Evol Biol 9:4. doi:10.1186/1471-2148-9-4

    PubMed Central  PubMed  Google Scholar 

  • Hulbert AJ (1980) The evolution of energy metabolism in mammals. In: Schmidt-Nielsen K, Bolis L, Taylor C (eds) Comparative physiology: primitive mammals. Cambridge University Press, Cambridge, pp 129–139

    Google Scholar 

  • IUPS-Thermal-Commission (2003) Glossary of terms for thermal physiology. J Therm Biol 28:75–106. doi:10.1016/S0306-4565(02)00055-4

    Google Scholar 

  • Jamieson L, Stribling D, Rothwell NJ, Stock MJ (1984) Effect of noradrenaline on oxygen consumption and tissue blood flow in young pigs. Can J Physiol Pharmacol 62:136–141

    CAS  PubMed  Google Scholar 

  • Janský L (1969) Comparative aspects of cold acclimation and nonshivering thermogenesis in homeotherms. Int J Biometeorol 13:199–209

    PubMed  Google Scholar 

  • Janský L (1973) Non-shivering thermogenesis and its thermoregulatory significance. Biol Rev Camb Philos Soc 48:85–132

    PubMed  Google Scholar 

  • Janský L, Hart JS (1963) Participation of skeletal muscle and kidney during nonshivering thermogenesis in cold-acclimated rats. Can J Biochem Physiol 41:953–964. doi:10.1139/o63-108

    PubMed  Google Scholar 

  • Jastroch M, Withers K, Klingenspor M (2004) Uncoupling protein 2 and 3 in marsupials: identification, phylogeny, and gene expression in response to cold and fasting in Antechinus flavipes. Physiol Genomics 17:130–139. doi:10.1152/physiolgenomics.00165.2003

    CAS  PubMed  Google Scholar 

  • Jastroch M, Wuertz S, Kloas W, Klingenspor M (2005) Uncoupling protein 1 in fish uncovers an ancient evolutionary history of mammalian nonshivering thermogenesis. Physiol Genomics 22:150–156. doi:10.1152/physiolgenomics.00070.2005

    CAS  PubMed  Google Scholar 

  • Jastroch M, Buckingham JA, Helwig M, Klingenspor M, Brand MD (2007) Functional characterization of UCP1 in the common carp: uncoupling activity in liver mitochondria and cold-induced expression in the brain. J Comp Physiol B 177:743–752. doi:10.1007/s00360-007-0171-6

    CAS  PubMed  Google Scholar 

  • Jastroch M, Withers KW, Taudien S, Frappell PB, Helwig M, Fromme T, Hirschberg V, Heldmaier G, McAllan BM, Firth BT, Burmester T, Platzer M, Klingenspor M (2008) Marsupial uncoupling protein 1 sheds light on the evolution of mammalian nonshivering thermogenesis. Physiol Genomics 32:161–169. doi:10.1152/physiolgenomics.00183.2007

    CAS  PubMed  Google Scholar 

  • Jastroch M, Divakaruni AS, Mookerjee S, Treberg JR, Brand MD (2010) Mitochondrial proton and electron leaks. Essays Biochem 47:53–67. doi:10.1042/bse0470053

    CAS  PubMed Central  PubMed  Google Scholar 

  • Jastroch M, Hirschberg V, Klingenspor M (2012) Functional characterization of UCP1 in mammalian HEK293 cells excludes mitochondrial uncoupling artefacts and reveals no contribution to basal proton leak. Biochim Biophys Acta 1817:1660–1670. doi:10.1016/j.bbabio.2012.05.014

    CAS  PubMed  Google Scholar 

  • Joly J, Saint-Girons H (1975) Influence de la température sur la vitesse de la esperematogènese, la durée de l’activité spermatogénétique et l’évolution des caractères secondaires du lézard des murailles, Lacerta muralis L. (Reptilia, Lacertidae). Arch Anat Microsc Morph Exp 64:317–336

    CAS  Google Scholar 

  • Kaciuba-Uściłko H, Poczopko P (1973) The effect of noradrenaline on heat production in the new-born pig. Experientia 29:108–109. doi:10.1007/BF01913283

    PubMed  Google Scholar 

  • Keipert S, Jastroch M (2014) Brite/beige fat and UCP1—is it thermogenesis? Biochim Biophys Acta 1837:1075–1082. doi:10.1016/j.bbabio.2014.02.008

    CAS  PubMed  Google Scholar 

  • Keipert S, Klaus S, Heldmaier G, Jastroch M (2010) UCP1 ectopically expressed in murine muscle displays native function and mitigates mitochondrial superoxide production. Biochim Biophys Acta 1797:324–330. doi:10.1016/j.bbabio.2009.11.008

    CAS  PubMed  Google Scholar 

  • Kim EB, Fang X, Fushan AA, Huang Z, Lobanov AV, Han L, Marino SM, Sun X, Turanov AA, Yang P, Yim SH, Zhao X, Kasaikina MV, Stoletzki N, Peng C, Polak P, Xiong Z, Kiezun A, Zhu Y, Chen Y, Kryukov GV, Zhang Q, Peshkin L, Yang L et al (2011) Genome sequencing reveals insights into physiology and longevity of the naked mole rat. Nature 479:223–227. doi:10.1038/nature10533

    CAS  PubMed Central  PubMed  Google Scholar 

  • Klaus S, Heldmaier G, Ricquier D (1988) Seasonal acclimation of bank voles and wood mice: nonshivering thermogenesis and thermogenic properties of brown adipose tissue mitochondria. J Comp Physiol B 158:157–164

    CAS  PubMed  Google Scholar 

  • Klingenberg M, Huang SG (1999) Structure and function of the uncoupling protein from brown adipose tissue. Biochim Biophys Acta 1415:271–296

    CAS  PubMed  Google Scholar 

  • Klingenberg M, Winkler E (1985) The reconstituted isolated uncoupling protein is a membrane potential driven H+ translocator. EMBO J 4:3087–3092

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koteja P (2000) Energy assimilation, parental care and the evolution of endothermy. Proc Biol Sci 267:479–484. doi:10.1098/rspb.2000.1025

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koza RA, Hohmann SM, Guerra C, Rossmeisl M, Kozak, LP (2000) Synergistic gene interactions control the induction of the mitochondrial uncoupling protein (Ucp1) gene in white fat tissue. J Biol Chem 275:34486–34492. doi:10.1074/jbc.M002136200

  • Kozłowski J (1992) Optimal allocation of resources to growth and reproduction: implications for age and size at maturity. Trends Ecol Evol 7:15–19. doi:10.1016/0169-5347(92)90192-E

    PubMed  Google Scholar 

  • Kozłowski J, Weiner J (1997) Interspecific allometries are by-products of body size optimization. Am Nat 149:352–380. doi:10.2307/2463399

    Google Scholar 

  • Król E, Martin SAM, Huhtaniemi IT, Douglas A, Speakman JR (2011) Negative correlation between milk production and brown adipose tissue gene expression in lactating mice. J Exp Biol 214:4160–4170. doi:10.1242/jeb.061382

    PubMed  Google Scholar 

  • Kronfeld-Schor N, Haim A, Dayan T, Zisapel N, Klingenspor M, Heldmaier G (2000) Seasonal thermogenic acclimation of diurnally and nocturnally active desert spiny mice. Physiol Biochem Zool 73:37–44. doi:10.1086/316718

    CAS  PubMed  Google Scholar 

  • Laloi M, Klein M, Riesmeier JW, Müller-Röber B, Fleury C, Bouillaud F, Ricquier D (1997) A plant cold-induced uncoupling protein. Nature 389:135–136. doi:10.1038/38156

    CAS  PubMed  Google Scholar 

  • Lavocat R (1978) Rodentia and lagomorpha. In: Magio V, Cooke H (eds) Evolution of African mammals. Havard University Press, Cambridge, pp 68–89

    Google Scholar 

  • Lean MEJ (1989) Brown adipose tissue in humans. Proc Nutr Soc 48:243–256

    CAS  PubMed  Google Scholar 

  • Lee Y-H, Petkova AP, Mottillo EP, Granneman JG (2012) In vivo identification of bipotential adipocyte progenitors recruited by β3-adrenoceptor activation and high fat feeding. Cell Metab 15:480–491. doi:10.1016/j.cmet.2012.03.009

    CAS  PubMed Central  PubMed  Google Scholar 

  • Levesque DL, Lovegrove BG (2014) Increased homeothermy during reproduction in a basal placental mammal. J Exp Biol 217:1535–1542. doi:10.1242/jeb.098848

    PubMed  Google Scholar 

  • Levesque D, Lobban K, Lovegrove B (2014) Effects of reproductive status and high ambient temperatures on the body temperature of a free-ranging basoendotherm. J Comp Physiol B. doi:10.1007/s00360-014-0858-4

    PubMed  Google Scholar 

  • Li XS, Wang DH (2005) Seasonal adjustments in body mass and thermogenesis in Mongolian gerbils (Meriones unguiculatus): the roles of short photoperiod and cold. J Comp Physiol B 175:593–600. doi:10.1007/s00360-005-0022-2

    CAS  PubMed  Google Scholar 

  • Li Q, Sun R, Huang C, Wang Z, Liu X, Hou J, Liu J, Cai L, Li N, Zhang S, Wang Y (2001) Cold adaptive thermogenesis in small mammals from different geographical zones of China. Comp Biochem Physiol A Mol Integr Physiol 129:949–961

    CAS  PubMed  Google Scholar 

  • Licht P (1972) Actions of mammalian pituitary gonadotropins (FSH and LH) in reptiles. Gen Comp Endocrinol 19:282–289. doi:10.1016/0016-6480(72)90108-6

    CAS  PubMed  Google Scholar 

  • Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, Mussack T, Nilsson D, Romu T, Nuutila P, Virtanen KA, Beuschlein F, Persson A, Borga M, Enerbäck S (2013) Evidence for two types of brown adipose tissue in humans. Nat Med 19:631–634. doi:10.1038/nm.3017

    CAS  PubMed  Google Scholar 

  • Lin CS, Klingenberg M (1982) Characteristics of the isolated purine nucleotide binding protein from brown fat mitochondria. Biochemistry 21:2950–2956. doi:10.1021/bi00541a023

    CAS  PubMed  Google Scholar 

  • Loncar D, Afzelius BA, Cannon B (1988) Epididymal white adipose tissue after cold stress in rats. I. Nonmitochondrial changes. J Ultrastruct Mol Struct Res 101:109–122

    CAS  PubMed  Google Scholar 

  • Loudon A, Rothwell N, Stock M (1985) Brown fat, thermogenesis and physiological birth in a marsupial. Comp Biochem Physiol Part A Physiol 81:815–819. doi:10.1016/0300-9629(85)90912-0

    CAS  Google Scholar 

  • Lovegrove BG (2012a) The evolution of mammalian body temperature: the Cenozoic supraendothermic pulses. J Comp Physiol B 182:579–589. doi:10.1007/s00360-011-0642-7

    PubMed  Google Scholar 

  • Lovegrove BG (2012b) The evolution of endothermy in Cenozoic mammals: a plesiomorphic-apomorphic continuum. Biol Rev Camb Philos Soc 87:128–162. doi:10.1111/j.1469-185X.2011.00188.x

    PubMed  Google Scholar 

  • Lovegrove BG, Génin F (2008) Torpor and hibernation in a basal placental mammal, the lesser hedgehog tenrec Echinops telfairi. J Comp Physiol B 178:691–698. doi:10.1007/s00360-008-0257-9

    PubMed  Google Scholar 

  • Lovegrove BG, Heldmaier G, Knight M (1991) Seasonal and circadian energetic patterns in an arboreal rodent, Thallomys paedulcus, and a burrow-dwelling rodent, Aethomys namaquensis, from the Kalahari Desert. J Therm Biol 16:199–209. doi:10.1016/0306-4565(91)90026-X

    Google Scholar 

  • Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis. Nature 404:652–660. doi:10.1038/35007527

    CAS  PubMed  Google Scholar 

  • Luna F, Roca P, Oliver J, Antenucci CD (2012) Maximal thermogenic capacity and non-shivering thermogenesis in the South American subterranean rodent Ctenomys talarum. J Comp Physiol B 182:971–983. doi:10.1007/s00360-012-0675-6

    PubMed  Google Scholar 

  • Lynch GR, White S, Grundel R, Berger M (1978) Effects of photoperiod, melatonin administration and thyroid block on spontaneous daily torpor and temperature regulation in the white-footed mouse, Peromyscus leucopus. J Comp Physiol 125:157–163. doi:10.1007/BF00686752

    CAS  Google Scholar 

  • Maier HA, Feist DD (1991) Thermoregulation, growth, and reproduction in Alaskan collared lemmings: role of short day and cold. Am J Physiol 261:522–530

    Google Scholar 

  • McDevitt RM, Speakman JR (1996) Summer acclimatization in the short-tailed field vole, Microtus agrestis. J Comp Physiol B 166:286–293

    CAS  PubMed  Google Scholar 

  • McNab BK (1978) The evolution of endothermy in the phylogeny of mammals. Am Nat 112:1–21. doi:10.2307/2460134

    Google Scholar 

  • Merritt JF (1995) Seasonal thermogenesis and changes in body mass of Masked shrews, Sorex cinereus. J Mammal 76:1020–1035. doi:10.2307/1382596

    Google Scholar 

  • Merritt JF, Zegers DA (1991) Seasonal thermogenesis and body-mass dynamics of Clethrionomys gapperi. Can J Zool 69:2771–2777. doi:10.1139/z91-390

    Google Scholar 

  • Merritt JF, Zegers DA, Rose LR (2001) Seasonal thermogenesis of Southern flying squirrels (Glaucomys volans). J Mammal 82:51–64. doi:10.2307/1383679

    Google Scholar 

  • Mills EM, Banks ML, Sprague JE, Finkel T (2003) Pharmacology: uncoupling the agony from ecstasy. Nature 426:403–404

    CAS  PubMed  Google Scholar 

  • Miroux B, Frossard V, Raimbault S, Ricquier D, Bouillaud F (1993) The topology of the brown adipose tissue mitochondrial uncoupling protein determined with antibodies against its antigenic sites revealed by a library of fusion proteins. EMBO J 12:3739–3745

    CAS  PubMed Central  PubMed  Google Scholar 

  • Morrison SF, Madden CJ, Tupone D (2014) Central neural regulation of brown adipose tissue thermogenesis and energy expenditure. Cell Metab 19:741–756. doi:10.1016/j.cmet.2014.02.007

    CAS  PubMed Central  PubMed  Google Scholar 

  • Moshkin MP, Novikov EA, Petrovski DV (2011) Seasonal changes of thermoregulation in the mole vole Ellobius talpinus. Physiol Biochem Zool 74:869–875. doi:10.1086/324750

    Google Scholar 

  • Mount (1968) The climatic physiology of the pig. The Camelot Press, London and Southampton, p 76

  • Mouroux I, Bertin R, Portet R (1990) Thermogenic capacity of the brown adipose tissue of developing rats; effects of rearing temperature. J Dev Physiol 14:337–342

    CAS  PubMed  Google Scholar 

  • Murphy WJ, Eizirik E, O’Brien SJ, Madsen O, Scally M, Douady CJ, Teeling E, Ryder OA, Stanhope MJ, de Jong WW, Springer MS (2001) Resolution of the early placental mammal radiation using Bayesian phylogenetics. Science 294:2348–2351. doi:10.1126/science.1067179

    CAS  PubMed  Google Scholar 

  • Mzilikazi N, Lovegrove BG (2006) Noradrenalin induces thermogenesis in a phylogenetically ancient eutherian mammal, the rock elephant shrew, Elephantulus myurus. J Comp Physiol B 176:75–84. doi:10.1007/s00360-005-0035-x

    CAS  PubMed  Google Scholar 

  • Mzilikazi N, Lovegrove BG, Ribble DO (2002) Exogenous passive heating during torpor arousal in free-ranging rock elephant shrews, Elephantulus myurus. Oecologia 133:307–314. doi:10.2307/4223422

    Google Scholar 

  • Mzilikazi N, Jastroch M, Meyer CW, Klingenspor M (2007) The molecular and biochemical basis of nonshivering thermogenesis in an African endemic mammal, Elephantulus myurus. Am J Physiol Regul Integr Comp Physiol 293:2120–2127. doi:10.1152/ajpregu.00427.2007

    Google Scholar 

  • Nagasaka T, Carlson L (1965) Responses of cold- and warm-adapted dogs to infused norepinephrine and acute body cooling. Am J Physiol 209:227–230

    CAS  PubMed  Google Scholar 

  • Nakamura K, Morrison SF (2008) A thermosensory pathway that controls body temperature. Nat Neurosci 11:62–71. doi:10.1038/nn2027

    CAS  PubMed Central  PubMed  Google Scholar 

  • Nautiyal KM, Dailey M, Brito N, Brito MNDA, Harris RB, Bartness TJ, Grill HJ (2008) Energetic responses to cold temperatures in rats lacking forebrain-caudal brain stem connections. Am J Physiol Regul Integr Comp Physiol 295:789–798. doi:10.1152/ajpregu.90394.2008

    Google Scholar 

  • Nedergaard J, Cannon B (2003) The “novel” “uncoupling” proteins UCP2 and UCP3: what do they really do? Pros and cons for suggested functions. Exp Physiol 88:65–84

    CAS  PubMed  Google Scholar 

  • Nedergaard J, Cannon B (2013a) How brown is brown fat? It depends where you look. Nat Med 19:540–541. doi:10.1038/nm.3187

    CAS  PubMed  Google Scholar 

  • Nedergaard J, Cannon B (2013b) UCP1 mRNA does not produce heat. Biochim Biophys Acta 1831:943–949. doi:10.1016/j.bbalip.2013.01.009

    CAS  PubMed  Google Scholar 

  • Nedergaard J, Cannon B (2014) The browning of white adipose tissue: some burning issues. Cell Metab 20:396–407. doi:10.1016/j.cmet.2014.07.005

    CAS  PubMed  Google Scholar 

  • Nedergaard J, Connolly E, Cannon B (1986) Brown adipose tissue in the mammalian neonate. In: Trayhurn P, Nicholls D (eds) Brown adipose tissue. Arnold, London, pp 152–213

    Google Scholar 

  • Nedergaard J, Bengtsson T, Cannon B (2007) Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 293:444–452. doi:10.1152/ajpendo.00691.2006

    Google Scholar 

  • Nespolo R, Opazo J, Rosenmann M, Bozinovic F (1999) Thermal acclimation, maximum metabolic rate and non-shivering thermogenesis of Phylottis xanthopygus (Rodentia) in the Andes mountains. J Mammal 80:742–748

    Google Scholar 

  • Nespolo RF, Bacigalupe LD, Rezende EL, Bozinovic F (2001) When nonshivering thermogenesis equals maximum metabolic rate: thermal acclimation and phenotypic plasticity of fossorial Spalacopus cyanus (Rodentia). Physiol Biochem Zool 74:325–332. doi:10.1086/320420

    CAS  PubMed  Google Scholar 

  • Nibbelink M, Moulin K, Arnaud E, Duval C, Pénicaud L, Casteilla L (2001) Brown fat UCP1 is specifically expressed in uterine longitudinal smooth muscle cells. J Biol Chem 276:47291–47295

    CAS  PubMed  Google Scholar 

  • Nicholls DG, Locke RM (1984) Thermogenic mechanisms in brown fat. Physiol Rev 64:1–64

    CAS  PubMed  Google Scholar 

  • Nicol SC (1978) Non-shivering thermogenesis in the potoroo, Potorous tridactylus (Kerr). Comp Biochem Physiol Part C Comp Pharmacol 59:33–37. doi:10.1016/0306-4492(78)90008-4

    CAS  Google Scholar 

  • Nicol SC, Pavlides D, Andersen NA (1997) Nonshivering thermogenesis in marsupials: absence of thermogenic response to beta 3-adrenergic agonists. Comp Biochem Physiol A Physiol 117:399–405

    CAS  PubMed  Google Scholar 

  • Nicol SC, Andersen NA, Arnold W, Ruf T (2009) Rewarming rates of two large hibernators: comparison of a monotreme and a eutherian. J Therm Biol 34:155–159. doi:10.1016/j.jtherbio.2009.01.003

    Google Scholar 

  • Nowack J, Dausmann KH, Mzilikazi N (2013) Nonshivering thermogenesis in the African lesser bushbaby, Galago moholi. J Exp Biol 216:3811–3817. doi:10.1242/jeb.089433

    PubMed  Google Scholar 

  • Oelkrug R, Kutschke M, Meyer CW, Heldmaier G, Jastroch M (2010) Uncoupling protein 1 decreases superoxide production in brown adipose tissue mitochondria. J Biol Chem 285:21961–21968

    CAS  PubMed Central  PubMed  Google Scholar 

  • Oelkrug R, Heldmaier G, Meyer CW (2011) Torpor patterns, arousal rates, and temporal organization of torpor entry in wildtype and UCP1-ablated mice. J Comp Physiol B 181:137–145. doi:10.1007/s00360-010-0503-9

    CAS  PubMed  Google Scholar 

  • Oelkrug R, Meyer CW, Heldmaier G, Mzilikazi N (2012) Seasonal changes in thermogenesis of a free-ranging afrotherian small mammal, the Western rock elephant shrew (Elephantulus rupestris). J Comp Physiol B 182:715–727. doi:10.1007/s00360-012-0647-x

    PubMed  Google Scholar 

  • Oelkrug R, Goetze N, Exner C, Lee Y, Ganjam GK, Kutschke M, Müller S, Stöhr S, Tschöp MH, Crichton PG, Heldmaier G, Jastroch M, Meyer CW (2013) Brown fat in a protoendothermic mammal fuels eutherian evolution. Nat Commun 4:2140

    PubMed Central  PubMed  Google Scholar 

  • Oelkrug R, Goetze N, Meyer CW, Jastroch M (2014) Antioxidant properties of UCP1 are evolutionarily conserved in mammals and buffer mitochondrial reactive oxygen species. Free Radic Biol Med 77:210–216. doi:10.1016/j.freeradbiomed.2014.09.004

    CAS  PubMed  Google Scholar 

  • Opazo JC, Nespolo RF, Bozinovic F (1999) Arousal from torpor in the Chilean mouse-opposum (Thylamys elegans): does non-shivering thermogenesis play a role? Comp Biochem Physiol A Mol Integr Physiol 123:393–397

    CAS  PubMed  Google Scholar 

  • Polymeropoulos ET, Jastroch M, Frappell PB (2012) Absence of adaptive nonshivering thermogenesis in a marsupial, the fat-tailed dunnart (Sminthopsis crassicaudata). J Comp Physiol B 182:393–401. doi:10.1007/s00360-011-0623-x

    CAS  PubMed  Google Scholar 

  • Pope M, Budge H, Symonds ME (2014) The developmental transition of ovine adipose tissue through early life. Acta Physiol 210:20–30. doi:10.1111/apha.12053

    CAS  Google Scholar 

  • Poppitt SD, Speakman JR, Racey PA (1994) Energetics of reproduction in the lesser hedgehog tenrec, Echinops telfairi (Martin). Physiol Zool 67:976–994. doi:10.2307/30163874

    Google Scholar 

  • Raimbault S, Dridi S, Denjean F, Lachuer J, Couplan E, Bouillaud F, Bordas A, Duchamp C, Taouis M, Ricquier D (2001) An uncoupling protein homologue putatively involved in facultative muscle thermogenesis in birds. Biochem J 353:441–444

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rasmussen AT (1923) The so-called hibernating gland. J Morphol 38:147–205. doi:10.1002/jmor.1050380106

    Google Scholar 

  • Richter TA, Webb PI, Skinner JD (1997) Limits to the distribution of the southern African ice rat (Otomys sloggetti): thermal physiology or competitive exclusion? Funct Ecol 11:240–246. doi:10.1046/j.1365-2435.1997.00078.x

    Google Scholar 

  • Rodriguez-Serrano E, Bozinovic F (2009) Interplay between global patterns of environmental temperature and variation in nonshivering thermogenesis of rodent species across large spatial scales. Glob Chang Biol 15:2116–2122. doi:10.1111/j.1365-2486.2009.01854.x

    Google Scholar 

  • Rose RW, Kuswanti N, Colquhoun EQ (1998) Development of endothermy in a Tasmanian marsupial, Bettongia gaimardi and its response to cold and noradrenaline. J Comp Physiol B 168:359–363

    CAS  PubMed  Google Scholar 

  • Rose RW, West AK, Ye JM, McCormick GH, Colquhoun EQ (1999) Nonshivering thermogenesis in a marsupial (the tasmanian bettong Bettongia gaimardi) is not attributable to brown adipose tissue. Physiol Biochem Zool 72:699–704. doi:10.1086/316709

    CAS  PubMed  Google Scholar 

  • Rosenwald M, Perdikari A, Rülicke T, Wolfrum C (2013) Bi-directional interconversion of brite and white adipocytes. Nat Cell Biol 15:659–667

    CAS  PubMed  Google Scholar 

  • Rothwell NJ, Stock MJ (1985a) Biological distribution and significance of brown adipose tissue. Comp Biochem Physiol A Comp Physiol 82:745–751

    CAS  PubMed  Google Scholar 

  • Rothwell NJ, Stock MJ (1985b) Thermogenic capacity and brown adipose tissue activity in the common marmoset. Comp Biochem Physiol A Comp Physiol 81:683–686

    CAS  PubMed  Google Scholar 

  • Rousset S, Alves-Guerra MC, Ouadghiri-Bencherif S, Kozak LP, Miroux B, Richard D, Bouillaud F, Ricquier D, Cassard-Doulcier AM (2003) Uncoupling Protein 2, but not uncoupling protein 1, is expressed in the female mouse reproductive tract. J Biol Chem 278:45843–45847

    CAS  PubMed  Google Scholar 

  • Rousset S, Alves-Guerra M-C, Mozo J, Miroux B, Cassard-Doulcier A-M, Bouillaud F, Ricquier D (2004) The biology of mitochondrial uncoupling proteins. Diabetes 53:130–135

    Google Scholar 

  • Rowlatt U, Mrosovsky N, English A (1971) A comparative survey of brown fat in the neck and axilla of mammals at birth. Biol Neonate 17:53–83

    CAS  PubMed  Google Scholar 

  • Ruben J (1995) The evolution of endothermy in mammals and birds: from physiology to fossils. Annu Rev Physiol 57:69–95. doi:10.1146/annurev.ph.57.030195.000441

    CAS  PubMed  Google Scholar 

  • Saarela S, Hissa R (1993) Metabolism, thermogenesis and daily rhythm of body temperature in the wood lemming, Myopus schisticolor. J Comp Physiol B 163:546–555

    CAS  PubMed  Google Scholar 

  • Scantlebury M, Afik D, Shanas U, Haim A (2002) Comparative non-shivering thermogenesis in adjacent populations of the common spiny mouse (Acomys cahirinus) from opposite slopes: the effects of increasing salinity. J Comp Physiol B 172:1–5

    PubMed  Google Scholar 

  • Scantlebury M, Shanas U, Kupshtein H, Afik D, Haim A (2003) Non-shivering thermogenesis in common spiny mice Acomys cahirinus from adjacent habitats: response to seasonal acclimatization and salinity acclimation. J Therm Biol 28:287–293. doi:10.1016/S0306-4565(03)00005-6

    Google Scholar 

  • Scantlebury M, Lovegrove BG, Jackson CR, Bennett NC, Lutermann H (2008) Hibernation and non-shivering thermogenesis in the Hottentot golden mole (Amblysomus hottentottus longiceps). J Comp Physiol B 178:887–897. doi:10.1007/s00360-008-0277-5

    CAS  PubMed  Google Scholar 

  • Scholander PF, Walters V, Hock R, Irving L (1950) Body insulation of some arctic and tropical mammals and birds. Biol Bull 99:225–236

    CAS  PubMed  Google Scholar 

  • Scholl P (1974) Temperaturregulation beim madegassischen Igeltanrek Echinops telfairi (Martin, 1838). J Comp Physiol B 89:175–195

    Google Scholar 

  • Schulz TJ, Huang P, Huang TL, Xue R, McDougall LE, Townsend KL, Cypess AM, Mishina Y, Gussoni E, Tseng YH (2013) Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature 495:379–383. doi:10.1038/nature11943

    CAS  PubMed Central  PubMed  Google Scholar 

  • Shabalina IG, Jacobsson A, Cannon B, Nedergaard J (2004) Native UCP1 displays simple competitive kinetics between the regulators purine nucleotides and fatty acids. J Biol Chem 279:38236–38248. doi:10.1074/jbc.M402375200

    CAS  PubMed  Google Scholar 

  • Shabalina IG, Petrovic N, de Jong JMA, Kalinovich AV, Cannon B, Nedergaard J (2013) UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep 5:1196–1203. doi:10.1016/j.celrep.2013.10.044

    CAS  PubMed  Google Scholar 

  • Smith BK, Dawson TJ (1984) Changes in the thermal balance of a marsupial (Dasyuroides byrnei) during cold and warm acclimation. J Therm Biol 9:199–204. doi:10.1016/0306-4565(84)90022-6

    Google Scholar 

  • Smith R, Hock R (1963) Brown fat: thermogenic effector of arousal in hibernators. Science 140:199–200

    CAS  PubMed  Google Scholar 

  • Smith B, Horwitz R (1969) Brown fat and thermogenesis. Physiol Rev 49:330–425

    CAS  PubMed  Google Scholar 

  • Smith R, Roberts J (1964) Thermogenesis of brown adipose tissue in cold-acclimated rats. Am J Physiol 206:143–148

    CAS  PubMed  Google Scholar 

  • Sparti A (1992) Thermogenic sapacity of shrews (Mammalia, Soricidae) and its relationship with basal rate of metabolism. Physiol Zool 65:77–96. doi:10.2307/30158240

    Google Scholar 

  • Springer MS, Cleven GC, Madsen O, de Jong WW, Waddell VG, Amrine HM, Stanhope MJ (1997) Endemic African mammals shake the phylogenetic tree. Nature 388:61–64. doi:10.1038/40386

    CAS  PubMed  Google Scholar 

  • Stearns S (1992) The evolution of life histories. Oxford University Press, Oxford

    Google Scholar 

  • Stier A, Bize P, Habold C, Bouillaud F, Massemin S, Criscuolo F (2014) Mitochondrial uncoupling prevents cold-induced oxidative stress: a case study using UCP1 knockout mice. J Exp Biol 217:624–630. doi:10.1242/jeb.092700

    CAS  PubMed  Google Scholar 

  • Sundin U, Herron D, Cannon B (1981) Brown fat thermoregulation in developing hamsters (Mesocricetus auratus): a GDP-binding study. Biol Neonate 39:142–149

    CAS  PubMed  Google Scholar 

  • Sundin U, Moore G, Nedergaard J, Cannon B (1987) Thermogenin amount and activity in hamster brown fat mitochondria: effect of cold acclimation. Am J Physiol 252:822–832

    Google Scholar 

  • Symonds ME, Andrews DC, Buss DS et al (1996) Effect of rearing temperature on perirenal adipose tissue development and thermoregulation following methimazole treatment of postnatal lambs. Exp Physiol 81:995–1006

    CAS  PubMed  Google Scholar 

  • Thompson GE, Jenkinson DM (1969) Nonshivering thermogenesis in the newborn lamb. Can J Physiol Pharmacol 47:249–253

    CAS  PubMed  Google Scholar 

  • Thundathil JC, Rajamanickam GD, Kastelic JP, Newton LD (2012) The effects of increased testicular temperature on testis-specific isoform of Na+/K+-ATPase in sperm and its role in spermatogenesis and sperm function. Reprod Domest Anim 47:170–177. doi:10.1111/j.1439-0531.2012.02072.x

    PubMed  Google Scholar 

  • Tine M, Kuhl H, Jastroch M, Reinhardt R (2012) Genomic characterization of the European sea bass Dicentrarchus labrax reveals the presence of a novel uncoupling protein (UCP) gene family member in the teleost fish lineage. BMC Evol Biol 12:62. doi:10.1186/1471-2148-12-62

    CAS  PubMed Central  PubMed  Google Scholar 

  • Trayhurn P (1983) Decreased capacity for non-shivering thermogenesis during lactation in mice. Pflügers Arch 398:264–265. doi:10.1007/BF00657164

    CAS  PubMed  Google Scholar 

  • Trayhurn P, Wusteman MC (1987) Sympathetic activity in brown adipose tissue in lactating mice. Am J Physiol 253:515–520

    Google Scholar 

  • Trayhurn P, Douglas JB, McGuckin MM (1982) Brown adipose tissue thermogenesis is “suppressed” during lactation in mice. Nature 298:59–60

    CAS  PubMed  Google Scholar 

  • Trayhurn P, Temple NJ, Van Aerde J (1989) Evidence from immunoblotting studies on uncoupling protein that brown adipose tissue is not present in the domestic pig. Can J Physiol Pharmacol 67:1480–1485

    CAS  PubMed  Google Scholar 

  • Trzcionka M, Withers KW, Klingenspor M, Jastroch M (2008) The effects of fasting and cold exposure on metabolic rate and mitochondrial proton leak in liver and skeletal muscle of an amphibian, the cane toad Bufo marinus. J Exp Biol 211:1911–1918. doi:10.1242/jeb.016519

    CAS  PubMed  Google Scholar 

  • Ussar S, Lee KY, Dankel SN, Boucher J, Haering MF, Kleinridders A, Thomou T, Xue R, Macotela Y, Cypess AM, Tseng YH, Mellgren G, Kahn CR (2014) ASC-1, PAT2, and P2RX5 are cell surface markers for white, beige, and brown adipocytes. Sci Transl Med 6:247ra103. doi:10.1126/scitranslmed.3008490

  • Van der Lans AAJJ, Wierts R, Vosselman MJ, Schrauwen P, Brans B, van Marken Lichtenbelt WD (2014) Cold-activated brown adipose tissue in human adults: methodological issues. Am J Physiol Regul Integr Comp Physiol 307:R103–R113. doi:10.1152/ajpregu.00021.2014

    PubMed  Google Scholar 

  • Van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JMAFL, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360:1500–1508. doi:10.1056/NEJMoa0808718

    PubMed  Google Scholar 

  • Vatnick I, Tyzbir RS, Welch JG, Hooper AP (1987) Regression of brown adipose tissue mitochondrial function and structure in neonatal goats. Am J Physiol 252:391–395

    Google Scholar 

  • Vaughan T, Ryan J, Czaplewski N (2000) Mammalogy, 4th edn. Saunders College Publishing

  • Vianna CR, Hagen T, Zhang CY, Bachman E, Boss O, Gereben B, Moriscot AS, Lowell BB, Bicudo JE, Bianco AC (2001) Cloning and functional characterization of an uncoupling protein homolog in hummingbirds. Physiol Genomics 5:137–145

    CAS  PubMed  Google Scholar 

  • Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360:1518–1525. doi:10.1056/NEJMoa0808949

    CAS  PubMed  Google Scholar 

  • Wang D, Sun R, Wang Z, Liu J (1999) Effects of temperature and photoperiod on thermogenesis in plateau pikas (Ochotona curzoniae) and root voles (Microtus oeconomus). J Comp Physiol B 169:77–83

    CAS  PubMed  Google Scholar 

  • Warnecke L, Geiser F (2010) The energetics of basking behaviour and torpor in a small marsupial exposed to simulated natural conditions. J Comp Physiol B 180:437–445. doi:10.1007/s00360-009-0417-6

    PubMed  Google Scholar 

  • Warnecke L, Turner JM, Geiser F (2008) Torpor and basking in a small arid zone marsupial. Naturwissenschaften 95:73–78. doi:10.1007/s00114-007-0293-4

    CAS  PubMed  Google Scholar 

  • Warren WC, Hillier LW, Marshall GJ, Birney E, Ponting CP, Grützner F, Belov K, Miller W, Clarke L, Chinwalla AT, Yang SP, Heger A, Locke DP, Miethke P, Waters PD, Veyrunes F, Fulton L, Fulton B, Graves T, Wallis J et al (2008) Genome analysis of the platypus reveals unique signatures of evolution. Nature 453:175–183. doi:10.1038/nature06936

    CAS  PubMed Central  PubMed  Google Scholar 

  • Webster AJF, Heitman JH, Hays FL, Olynyk GP (1969) Catecholamines and cold thermogenesis in sheep. Can J Physiol Pharmacol 47:719–724. doi:10.1139/y69-122

    CAS  PubMed  Google Scholar 

  • Woodley R, Buffenstein R (2002) Thermogenic changes with chronic cold exposure in the naked mole-rat (Heterocephalus glaber). Comp Biochem Physiol A Mol Integr Physiol 133:827–834

    PubMed  Google Scholar 

  • Wu J, Boström P, Sparks LM, Ye L, Choi JH, Giang AH, Khandekar M, Virtanen KA, Nuutila P, Schaart G, Huang K, Tu H, van Marken Lichtenbelt WD, Hoeks J, Enerbäck S, Schrauwen P, Spiegelman BM (2012) Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell 150:366–376. doi:10.1016/j.cell.2012.05.016

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wu J, Cohen P, Spiegelman BM (2013) Adaptive thermogenesis in adipocytes : is beige the new brown? Genes Dev 27:234–250. doi:10.1101/gad.211649.112.from

    CAS  PubMed Central  PubMed  Google Scholar 

  • Wunder B (1984) Strategies for, and environmental cueing mechanisms of, seasonal changes in thermoregulatory parameters of small mammals. In: Merrit J (ed) Winter ecology of small mammals. Carnegie Museum of Natural History special publication, Pittsburgh, pp 165–172

    Google Scholar 

  • Xue B, Coulter A, Rim JS, Koza RA, Kozak LP (2005) Transcriptional synergy and the regulation of Ucp1 during brown adipocyte induction in white fat depots. Mol Cell Biol 25:8311–8322. doi:10.1128/MCB.25.18.8311-8322.2005

    CAS  PubMed Central  PubMed  Google Scholar 

  • Xue B, Rim J-S, Hogan JC, Coulter AA, Koza RA, Kozak LP (2007) Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J Lipid Res 48:41–51

    CAS  PubMed  Google Scholar 

  • Yang DB, Li L, Wang LP, Chi QS, Hambly C, Wang DH, Speakman JR (2013) Limits to sustained energy intake. XIX. A test of the heat dissipation limitation hypothesis in Mongolian gerbils (Meriones unguiculatus). J Exp Biol 216:3358–3368. doi:10.1242/jeb.085233

    CAS  PubMed  Google Scholar 

  • Ye JM, Edwards SJ, Rose RW, Steen JT, Clark MG, Colquhoun EQ (1996) Alpha-adrenergic stimulation of thermogenesis in a rat kangaroo (Marsupialia, Bettongia gaimardi). Am J Physiol 271:586–592

    Google Scholar 

  • Young P, Arch JR, Ashwell M (1984) Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Lett 167:10–14

    CAS  PubMed  Google Scholar 

  • Zegers D, Merrit J (1988) Effect of photoperiod and ambient temperature on non-shivering thermogenesis of Peromyscus maniculatus. Acta Theriol 33:273–281

    Google Scholar 

  • Zeisberger E, Brück K (1967) Quantitative Beziehungen zwischen Noradrenalin-Effekt und Ausmaß der zitterfreien Thermogenese beim Meerschweinchen. Pflügers Arch ges Physiol 296:263–275

    CAS  Google Scholar 

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Acknowledgments

We would like to thank G. Heldmaier for editorial communication of this invited review. We also thank four critical anonymous reviewers for suggestions to improve the quality of this manuscript, and Silke Morin, Stacey Leigh Webb, Drs. Susanne Keipert and Carola Meyer for critical reading and editing.

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  1. R. Oelkrug

    Present address: Institute of Pharmacology and Toxicology, Biomedical Center, University of Bonn, Sigmund-Freud-Straße 25, 53105, Bonn, Germany

Authors and Affiliations

  1. Department of Animal Physiology, Faculty of Biology, Philipps-Universität Marburg, Karl-von-Frisch Straße 8, 35043, Marburg, Germany

    R. Oelkrug

  2. CSIRO Marine and Atmospheric Research, Food Futures Flagship, GPO Box 1538, Hobart, TAS, 7001, Australia

    E. T. Polymeropoulos

  3. Institute for Diabetes and Obesity, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Munich, Germany

    M. Jastroch

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Oelkrug, R., Polymeropoulos, E.T. & Jastroch, M. Brown adipose tissue: physiological function and evolutionary significance. J Comp Physiol B 185, 587–606 (2015). https://doi.org/10.1007/s00360-015-0907-7

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