Skip to main content

Brown Adipose Tissue

  • Chapter
  • First Online:
Book cover Adipose Tissue Biology

Abstract

A constant body temperature can only be maintained when the rate of heat dissipation equals the rate of heat loss. Thermoregulatory heat production mechanisms compensating heat loss are classically categorized as shivering and non-shivering thermogenesis. Non-shivering thermogenesis occurs in brown adipose tissue, a unique heater organ only found in mammals. In brown adipose tissue mitochondria, the proton motive force across the inner membrane is dissipated as heat rather than converted to ATP. This tightly regulated process is catalyzed by the uncoupling protein 1. Non-shivering thermogenesis is elicited by the sympathetic innervation from hypothalamic and brain stem control regions which are activated by cold sensation. In a cold environment, up to half of the metabolic rate of rodents can be attributed to non-shivering thermogenesis in brown adipose tissue. The high thermogenic capacity of brown adipose tissue recruited in the defense of normothermia may also play a role in the regulation of energy balance in the face of hypercaloric nutrition. In this light, the recent discovery of significant amounts of metabolically active brown adipose tissue in healthy adult humans reintroduces an old player in human energy balance research and may enable new strategies to prevent excess body fat accumulation in man.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Notes

  1. 1.

    Dorsum præpingue habent, quũ cæteræ corporis partes sint macræ. Quand3 hæc vere nec pinguitudo nec caro dici potest: sed ut mamillarũ caro in bubus, inter eas est medium quidda.

References

  • 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(9):2369–2376

    PubMed  CAS  Google Scholar 

  • Asano A, Morimatsu M, Nikami H, Yoshida T, Saito M (1997) Adrenergic activation of vascular endothelial growth factor mRNA expression in rat brown adipose tissue: implication in cold-induced angiogenesis. Biochem J 328(Pt 1):179–183

    PubMed  CAS  Google Scholar 

  • Astrup A, Bulow J, Christensen NJ, Madsen J (1984) Ephedrine-induced thermogenesis in man: no role for interscapular brown adipose tissue. Clin Sci (Lond) 66(2):179–186

    CAS  Google Scholar 

  • Au-Yong IT, Thorn N, Ganatra R, Perkins AC, Symonds ME (2009) Brown adipose tissue and seasonal variation in humans. Diabetes 58(11):2583–2587

    Article  PubMed  CAS  Google Scholar 

  • Bamshad M, Song CK, Bartness TJ (1999) CNS origins of the sympathetic nervous system outflow to brown adipose tissue. Am J Physiol 276(6 Pt 2):R1569–R1578

    PubMed  CAS  Google Scholar 

  • Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, Giacobino JP, De MR, Cinti S (2010) The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab 298(6):E1244–E1253

    Article  PubMed  CAS  Google Scholar 

  • Bargmann W, Vonhehn G, Lindner E (1968) Cells of brown adipose tissue and its innervation. Z Zellforsch Mikrosk Anat 85(4):601

    Article  PubMed  CAS  Google Scholar 

  • Bartness TJ, Vaughan CH, Song CK (2010) Sympathetic and sensory innervation of brown adipose tissue. Int J Obes (Lond) 34(Suppl 1):S36–S42

    Article  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(8):e129

    Article  PubMed  CAS  Google Scholar 

  • Bouillaud F, Weissenbach J, Ricquier D (1986) Complete cDNA-derived amino acid sequence of rat brown fat uncoupling protein. J Biol Chem 261(4):1487–1490

    PubMed  CAS  Google Scholar 

  • Bukowiecki L, Collet AJ, Follea N, Guay G, Jahjah L (1982) Brown adipose tissue hyperplasia: a fundamental mechanism of adaptation to cold and hyperphagia. Am J Physiol 242(6):E353–E359

    PubMed  CAS  Google Scholar 

  • Canettieri G, Celi FS, Baccheschi G, Salvatori L, Andreoli M, Centanni M (2000) Isolation of human type 2 deiodinase gene promoter and characterization of a functional cyclic adenosine monophosphate response element. Endocrinology 141(5):1804–1813

    Article  PubMed  CAS  Google Scholar 

  • Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84(1):277–359

    Article  PubMed  CAS  Google Scholar 

  • Cao W, Daniel KW, Robidoux J, Puigserver P, Medvedev AV, Bai X, Floering LM, Spiegelman BM, Collins S (2004) p38 mitogen-activated protein kinase is the central regulator of cyclic AMP-dependent transcription of the brown fat uncoupling protein 1 gene. Mol Cell Biol 24(7):3057–3067

    Article  PubMed  CAS  Google Scholar 

  • Carroll AM, Haines LR, Pearson TW, Brennan C, Breen EP, Porter RK (2004) Immunodetection of UCP1 in rat thymocytes. Biochem Soc Trans 32(Pt 6):1066–1067

    PubMed  CAS  Google Scholar 

  • Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, Enerback S (2001) FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell 106(5):563–573

    Article  PubMed  CAS  Google Scholar 

  • Christensen CR, Clark PB, Morton KA (2006) Reversal of hypermetabolic brown adipose tissue in F-18 FDG PET imaging. Clin Nucl Med 31(4):193–196

    Article  PubMed  Google Scholar 

  • Cinti S (2005) The adipose organ. Prostaglandins Leukot Essent Fatty Acids 73(1):9–15

    Article  PubMed  CAS  Google Scholar 

  • Collins S, Kuhn CM, Petro AE, Swick AG, Chrunyk BA, Surwit RS (1996) Role of leptin in fat regulation. Nature 380(6576):677

    Article  PubMed  CAS  Google Scholar 

  • Cunningham S, Leslie P, Hopwood D, Illingworth P, Jung RT, Nicholls DG, Peden N, Rafael J, Rial E (1985) The characterization and energetic potential of brown adipose tissue in man. Clin Sci (Lond) 69(3):343–348

    CAS  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(15):1509–1517

    Article  PubMed  CAS  Google Scholar 

  • Daikoku T, Shinohara Y, Shima A, Yamazaki N, Terada H (1997) Dramatic enhancement of the specific expression of the heart-type fatty acid binding protein in rat brown adipose tissue by cold exposure. FEBS Lett 410(2–3):383–386

    Article  PubMed  CAS  Google Scholar 

  • De MR, Ricquier D, Cinti S (1998) TH-, NPY-, SP-, and CGRP-immunoreactive nerves in interscapular brown adipose tissue of adult rats acclimated at different temperatures: an immunohistochemical study. J Neurocytol 27(12):877–886

    Article  Google Scholar 

  • de Martinez MR, Scanlan TS, Obregon MJ (2010) The T3 receptor beta1 isoform regulates UCP1 and D2 deiodinase in rat brown adipocytes. Endocrinology 151(10):5074–5083

    Article  CAS  Google Scholar 

  • Enerback S (2010) Human brown adipose tissue. Cell Metab 11(4):248–252

    Article  PubMed  CAS  Google Scholar 

  • Enerback 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(6628):90–94

    Article  PubMed  CAS  Google Scholar 

  • Forner F, Kumar C, Luber CA, Fromme T, Klingenspor M, Mann M (2009) Proteome differences between brown and white fat mitochondria reveal specialized metabolic functions. Cell Metab 10(4):324–335

    Article  PubMed  CAS  Google Scholar 

  • Foster DO, Frydman ML (1978) Nonshivering thermogenesis in the rat. II. Measurements of blood flow with microspheres point to brown adipose tissue as the dominant site of the calorigenesis induced by noradrenaline. Can J Physiol Pharmacol 56(1):110–122

    Article  PubMed  CAS  Google Scholar 

  • Foster DO, Frydman ML (1979) Tissue distribution of cold-induced thermogenesis in conscious warm- or cold-acclimated rats reevaluated from changes in tissue blood flow: the dominant role of brown adipose tissue in the replacement of shivering by nonshivering thermogenesis. Can J Physiol Pharmacol 57(3):257–270

    Article  PubMed  CAS  Google Scholar 

  • Garlid KD, Orosz DE, Modriansky M, Vassanelli S, Jezek P (1996) On the mechanism of fatty acid-induced proton transport by mitochondrial uncoupling protein. J Biol Chem 271(5):2615–2620

    Article  PubMed  CAS  Google Scholar 

  • Gesner K (1551) Conradi Gesneri medici Tigurini historiae animalium lib. I. de quadrupedibus viviparis. apud Christ. Froschoverum, Tiguri, p 1

    Google Scholar 

  • Giordano A, Frontini A, Castellucci M, Cinti S (2004) Presence and distribution of cholinergic nerves in rat mediastinal brown adipose tissue. J Histochem Cytochem 52(7):923–930

    Article  PubMed  CAS  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(11):2048–2050

    PubMed  CAS  Google Scholar 

  • Golozoubova V, Gullberg H, Matthias A, Cannon B, Vennstrom B, Nedergaard J (2004) Depressed thermogenesis but competent brown adipose tissue recruitment in mice devoid of all hormone-binding thyroid hormone receptors. Mol Endocrinol 18(2):384–401

    Article  PubMed  CAS  Google Scholar 

  • Golozoubova V, Cannon B, Nedergaard J (2006) UCP1 is essential for adaptive adrenergic nonshivering thermogenesis. Am J Physiol Endocrinol Metab 291(2):E350–E357

    Article  PubMed  CAS  Google Scholar 

  • Hany TF, Gharehpapagh E, Kamel EM, Buck A, Himms-Hagen J, von Schulthess GK (2002) Brown adipose tissue: a factor to consider in symmetrical tracer uptake in the neck and upper chest region. Eur J Nucl Med Mol Imaging 29(10):1393–1398

    Article  PubMed  Google Scholar 

  • Heaton JM (1972) The distribution of brown adipose tissue in the human. J Anat 112(Pt 1):35–39

    PubMed  CAS  Google Scholar 

  • Heaton GM, Wagenvoord RJ, Kemp A Jr, Nicholls DG (1978) Brown-adipose-tissue mitochondria: photoaffinity labelling of the regulatory site of energy dissipation. Eur J Biochem 82(2):515–521

    Article  PubMed  CAS  Google Scholar 

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

    Article  Google Scholar 

  • Heldmaier G, Klingenspor M (2002) Role of photoperiod during seasonal acclimation of winter-active small mammals. In: Heldmaier G, Werner D (eds) Environmental signal processing and adaptation. Springer Verlag, Berlin, pp 251–279

    Chapter  Google Scholar 

  • Heldmaier G, Neuweiler G (2004) Vergleichende Tierphysiologie, 1st edn. Springer Verlag, Berlin, p 1

    Google Scholar 

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

    Google Scholar 

  • Himms-Hagen J (1979) Obesity may be due to a malfunctioning of brown fat. Can Med Assoc J 121(10):1361–1364

    PubMed  CAS  Google Scholar 

  • Hittelman KJ, Lindberg O, Cannon B (1969) Oxidative phosphorylation and compartmentation of fatty acid metabolism in brown fat mitochondria. Eur J Biochem 11(1):183–192

    Article  PubMed  CAS  Google Scholar 

  • Holm C (2003) Molecular mechanisms regulating hormone-sensitive lipase and lipolysis. Biochem Soc Trans 31(Pt 6):1120–1124

    Article  PubMed  CAS  Google Scholar 

  • Huang SG (2003) Binding of fatty acids to the uncoupling protein from brown adipose tissue mitochondria. Arch Biochem Biophys 412(1):142–146

    Article  PubMed  CAS  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

    Article  PubMed  CAS  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(2):150–156

    Article  PubMed  CAS  Google Scholar 

  • Jastroch M, Buckingham JA, Helwig M, Klingenspor M, Brand MD (2007) Functional characterisation of UCP1 in the common carp: uncoupling activity in liver mitochondria and cold-induced expression in the brain. J Comp Physiol B 177(7):743–752

    Article  PubMed  CAS  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(2):161–169

    PubMed  CAS  Google Scholar 

  • Kim SW, Her SJ, Kim SY, Shin CS (2005) Ectopic overexpression of adipogenic transcription factors induces transdifferentiation of MC3T3-E1 osteoblasts. Biochem Biophys Res Commun 327(3):811–819

    Article  PubMed  CAS  Google Scholar 

  • Kleiber M (1967) Der Energiehaushalt von Mensch und Haustier, 1st edn. Verlag Paul Parey, Berlin

    Google Scholar 

  • Klingenspor M (2003) Cold-induced recruitment of brown adipose tissue thermogenesis. Exp Physiol 88(1):141–148

    Article  PubMed  CAS  Google Scholar 

  • Klingenspor M, Ebbinghaus C, Hulshorst G, Stohr S, Spiegelhalter F, Haas K, Heldmaier G (1996a) Multiple regulatory steps are involved in the control of lipoprotein lipase activity in brown adipose tissue. J Lipid Res 37(8):1685–1695

    PubMed  CAS  Google Scholar 

  • Klingenspor M, Ivemeyer M, Wiesinger H, Haas K, Heldmaier G, Wiesner RJ (1996b) Biogenesis of thermogenic mitochondria in brown adipose tissue of Djungarian hamsters during cold adaptation. Biochem J 316(Pt 2):607–613

    PubMed  CAS  Google Scholar 

  • Konarzewski M, Diamond J (1994) Peak sustained metabolic-rate and its individual variation in cold-stressed mice. Physiol Zool 67(5):1186–1212

    Google Scholar 

  • Lafontan M, Berlan M (1993) Fat cell adrenergic receptors and the control of white and brown fat cell function. J Lipid Res 34(7):1057–1091

    PubMed  CAS  Google Scholar 

  • Ledesma A, de Lacoba MG, Arechaga I, Rial E (2002) Modeling the transmembrane arrangement of the uncoupling protein UCP1 and topological considerations of the nucleotide-binding site. J Bioenerg Biomembr 34(6):473–486

    Article  PubMed  CAS  Google Scholar 

  • Lee P, Greenfield JR, Ho KK, Fulham MJ (2010) A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 299(4):E601–E606

    Article  PubMed  CAS  Google Scholar 

  • Lin CS, Klingenberg M (1980) Isolation of the uncoupling protein from brown adipose tissue mitochondria. FEBS Lett 113(2):299–303

    Article  PubMed  CAS  Google Scholar 

  • Lopez M, Varela L, Vazquez MJ, Rodriguez-Cuenca S, Gonzalez CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, Martinez de Morentin PB, Tovar S, Nogueiras R, Carling D, Lelliott C, Gallego R, Oresic M, Chatterjee K, Saha AK, Rahmouni K, Dieguez C, Vidal-Puig A (2010) Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med 16(9):1001–1008

    Article  PubMed  CAS  Google Scholar 

  • Lowell BB, Spiegelman BM (2000) Towards a molecular understanding of adaptive thermogenesis. Nature 404(6778):652–660

    PubMed  CAS  Google Scholar 

  • Madsen L, Pedersen LM, Lillefosse HH, Fjaere E, Bronstad I, Hao Q, Petersen RK, Hallenborg P, Ma T, De MR, Araujo P, Mercader J, Bonet ML, Hansen JB, Cannon B, Nedergaard J, Wang J, Cinti S, Voshol P, Doskeland SO, Kristiansen K (2010) UCP1 induction during recruitment of brown adipocytes in white adipose tissue is dependent on cyclooxygenase activity. PLoS One 5(6):e11391

    Article  PubMed  CAS  Google Scholar 

  • Meyer CW, Willershauser M, Jastroch M, Rourke BC, Fromme T, Oelkrug R, Heldmaier G, Klingenspor M (2010) Adaptive thermogenesis and thermal conductance in wild-type and UCP1-KO mice. Am J Physiol Regul Integr Comp Physiol 299(5):R1396–R1406

    Article  PubMed  CAS  Google Scholar 

  • Morrison SF (2004) Central pathways controlling brown adipose tissue thermogenesis. News Physiol Sci 19:67–74

    Article  PubMed  Google Scholar 

  • Morrison SF, Nakamura K, Madden CJ (2008) Central control of thermogenesis in mammals. Exp Physiol 93(7):773–797

    Article  PubMed  Google Scholar 

  • Morton GJ, Cummings DE, Baskin DG, Barsh GS, Schwartz MW (2006) Central nervous system control of food intake and body weight. Nature 443(7109):289–295

    Article  PubMed  CAS  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(5):R2120–R2127

    Article  PubMed  CAS  Google Scholar 

  • Nakamura K, Morrison SF (2008) A thermosensory pathway that controls body temperature. Nat Neurosci 11(1):62–71

    Article  PubMed  CAS  Google Scholar 

  • Nautiyal KM, Dailey M, Brito N, Brito MN, 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(3):R789–R798

    Article  PubMed  CAS  Google Scholar 

  • Nedergaard J, Cannon B (2010) The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab 11(4):268–272

    Article  PubMed  CAS  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(2):E444–E452

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG (1974) Hamster brown-adipose-tissue mitochondria. The control of respiration and the proton electrochemical potential gradient by possible physiological effectors of the proton conductance of the inner membrane. Eur J Biochem 49(3):573–583

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG (1976) Hamster brown-adipose-tissue mitochondria. Purine nucleotide control of the ion conductance of the inner membrane, the nature of the nucleotide binding site. Eur J Biochem 62(2):223–228

    Article  PubMed  CAS  Google Scholar 

  • Nicholls DG (2001) A history of UCP1. Biochem Soc Trans 29(Pt 6):751–755

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Parker N, Crichton PG, Vidal-Puig AJ, Brand MD (2009) Uncoupling protein-1 (UCP1) contributes to the basal proton conductance of brown adipose tissue mitochondria. J Bioenerg Biomembr 41(4):335–342

    Article  PubMed  CAS  Google Scholar 

  • Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J (2010) Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 285(10):7153–7164

    Article  PubMed  CAS  Google Scholar 

  • Puchalski W, Bockler H, Heldmaier G, Langefeld M (1987) Organ blood flow and brown adipose tissue oxygen consumption during noradrenaline-induced nonshivering thermogenesis in the Djungarian hamster. J Exp Zool 242(3):263–271

    Article  PubMed  CAS  Google Scholar 

  • Rafael J, Ludolph HJ, Hohorst HJ (1969) Mitochondria from brown adipose tissue: uncoupling of respiratory chain phosphorylation by long fatty acids and recoupling by guanosine triphosphate. Hoppe Seylers Z Physiol Chem 350(9):1121–1131

    Article  PubMed  CAS  Google Scholar 

  • Rafael J, Vsiansky P, Heldmaier G (1985) Seasonal adaptation of brown adipose tissue in the Djungarian Hamster. J Comp Physiol B 155(4):521–528

    Article  PubMed  CAS  Google Scholar 

  • Rafael J, Pampel I, Wang X (1994) Effect of pH and MgCl2 on the binding of purine nucleotides to the uncoupling protein in membrane particles from brown fat mitochondria. Eur J Biochem 223(3):971–980

    Article  PubMed  CAS  Google Scholar 

  • Rehnmark S, Nedergaard J (1989) DNA synthesis in mouse brown adipose tissue is under beta-adrenergic control. Exp Cell Res 180(2):574–579

    Article  PubMed  CAS  Google Scholar 

  • Rial E, Zardoya R (2009) Oxidative stress, thermogenesis and evolution of uncoupling proteins. J Biol 8(6):58

    Article  PubMed  Google Scholar 

  • Ricquier D, Kader JC (1976) Mitochondrial protein alteration in active brown fat: a soidum dodecyl sulfate-polyacrylamide gel electrophoretic study. Biochem Biophys Res Commun 73(3):577–583

    Article  PubMed  CAS  Google Scholar 

  • Rim JS, Xue B, Gawronska-Kozak B, Kozak LP (2004) Sequestration of thermogenic transcription factors in the cytoplasm during development of brown adipose tissue. J Biol Chem 279(24):25916–25926

    Article  PubMed  CAS  Google Scholar 

  • Robidoux J, Kumar N, Daniel KW, Moukdar F, Cyr M, Medvedev AV, Collins S (2006) Maximal beta3-adrenergic regulation of lipolysis involves Src and epidermal growth factor receptor-dependent ERK1/2 activation. J Biol Chem 281(49):37794–37802

    Article  PubMed  CAS  Google Scholar 

  • Rolfe DF, Brand MD (1996) Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate. Am J Physiol Cell Physiol 271(4 Pt 1):C1380–C1389

    CAS  Google Scholar 

  • Rosen ED, MacDougald OA (2006) Adipocyte differentiation from the inside out. Nat Rev Mol Cell Biol 7(12):885–896

    Article  PubMed  CAS  Google Scholar 

  • Rothwell NJ, Stock MJ (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature 281(5726):31–35

    Article  PubMed  CAS  Google Scholar 

  • Saito S, Saito CT, Shingai R (2008) Adaptive evolution of the uncoupling protein 1 gene contributed to the acquisition of novel nonshivering thermogenesis in ancestral eutherian mammals. Gene 408(1–2):37–44

    Article  PubMed  CAS  Google Scholar 

  • Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, Iwanaga T, Miyagawa M, Kameya T, Nakada K, Kawai Y, Tsujisaki M (2009) High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes 58:1526–1531

    Article  PubMed  CAS  Google Scholar 

  • Schafer MK, Eiden LE, Weihe E (1998) Cholinergic neurons and terminal fields revealed by immunohistochemistry for the vesicular acetylcholine transporter. II. The peripheral nervous system. Neuroscience 84(2):361–376

    Article  PubMed  CAS  Google Scholar 

  • Scholander PF, Hock R, Walters V, Johnson F, Irving L (1950a) Heat regulation in some arctic and tropical mammals and birds. Biol Bull 99(2):237–258

    Article  PubMed  CAS  Google Scholar 

  • Scholander PF, Walters V, Hock R, Irving L (1950b) Body insulation of some arctic and tropical mammals and birds. Biol Bull 99(2):225–236

    Article  PubMed  CAS  Google Scholar 

  • Scholander PF, Hammel HT, Andersen KL, Loyning Y (1958) Metabolic acclimation to cold in man. J Appl Physiol 12(1):1–8

    PubMed  CAS  Google Scholar 

  • Seale P, Kajimura S, Yang W, Chin S, Rohas LM, Uldry M, Tavernier G, Langin D, Spiegelman BM (2007) Transcriptional control of brown fat determination by PRDM16. Cell Metab 6(1):38–54

    Article  PubMed  CAS  Google Scholar 

  • Seale P, Bjork B, Yang W, Kajimura S, Chin S, Kuang S, Scime A, Devarakonda S, Conroe HM, Erdjument-Bromage H, Tempst P, Rudnicki MA, Beier DR, Spiegelman BM (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454(7207):961–967

    Article  PubMed  CAS  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(37):38236–38248

    Article  PubMed  CAS  Google Scholar 

  • Shabalina IG, Ost M, Petrovic N, Vrbacky M, Nedergaard J, Cannon B (2010) Uncoupling protein-1 is not leaky. Biochim Biophys Acta 1797(6–7):773–784

    PubMed  CAS  Google Scholar 

  • Silva JE (2006) Thermogenic mechanisms and their hormonal regulation. Physiol Rev 86(2):435–464

    Article  PubMed  CAS  Google Scholar 

  • Skulachev VP (1991) Fatty acid circuit as a physiological mechanism of uncoupling of oxidative phosphorylation. FEBS Lett 294(3):158–162

    Article  PubMed  CAS  Google Scholar 

  • Smith RE (1961) Thermogenic activity of the hibernating gland in the cold-acclimated rat. Physiologist 4:113

    Google Scholar 

  • Smith RE, Roberts JC, Hittelman KJ (1966) Nonphosphorylating respiration of mitochondria from brown adipose tissue of rats. Science 154(749):653–654

    Article  PubMed  CAS  Google Scholar 

  • Soderlund V, Larsson SA, Jacobsson H (2007) Reduction of FDG uptake in brown adipose tissue in clinical patients by a single dose of propranolol. Eur J Nucl Med Mol Imaging 34(7):1018–1022

    Article  PubMed  CAS  Google Scholar 

  • Song CK, Vaughan CH, Keen-Rhinehart E, Harris RB, Richard D, Bartness TJ (2008) Melanocortin-4 receptor mRNA expressed in sympathetic outflow neurons to brown adipose tissue: neuroanatomical and functional evidence. Am J Physiol Regul Integr Comp Physiol 295(2):R417–R428

    Article  PubMed  CAS  Google Scholar 

  • Spiegelman BM, Flier JS (2001) Obesity and the regulation of energy balance. Cell 104(4):531–543

    Article  PubMed  CAS  Google Scholar 

  • Ste ML, Miura GI, Marsh DJ, Yagaloff K, Palmiter RD (2000) A metabolic defect promotes obesity in mice lacking melanocortin-4 receptors. Proc Natl Acad Sci USA 97(22):12339–12344

    Article  Google Scholar 

  • Stuart JA, Harper JA, Brindle KM, Jekabsons MB, Brand MD (2001) A mitochondrial uncoupling artifact can be caused by expression of uncoupling protein 1 in yeast. Biochem J 356(Pt 3):779–789

    Article  PubMed  CAS  Google Scholar 

  • Thonberg H, Fredriksson JM, Nedergaard J, Cannon B (2002) A novel pathway for adrenergic stimulation of cAMP-response-element-binding protein (CREB) phosphorylation: mediation via alpha1-adrenoceptors and protein kinase C activation. Biochem J 364(Pt 1):73–79

    PubMed  CAS  Google Scholar 

  • Thurlby PL, Trayhurn P (1980) Regional blood flow in genetically obese (ob/ob) mice. The importance of brown adipose tissue to the reduced energy expenditure on non-shivering thermogenesis. Pflugers Arch 385(3):193–201

    Article  PubMed  CAS  Google Scholar 

  • Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, Hamilton DL, Gimeno RE, Wahlestedt C, Baar K, Nedergaard J, Cannon B (2007) Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci USA 104(11):4401–4406

    Article  PubMed  CAS  Google Scholar 

  • Traut TW (1994) Physiological concentrations of purines and pyrimidines. Mol Cell Biochem 140(1):1–22

    Article  PubMed  CAS  Google Scholar 

  • Tseng YH, Kokkotou E, Schulz TJ, Huang TL, Winnay JN, Taniguchi CM, Tran TT, Suzuki R, Espinoza DO, Yamamoto Y, Ahrens MJ, Dudley AT, Norris AW, Kulkarni RN, Kahn CR (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454(7207):1000–1004

    Article  PubMed  CAS  Google Scholar 

  • Ukropec J, Anunciado RP, Ravussin Y, Hulver MW, Kozak LP (2006) UCP1-independent thermogenesis in white adipose tissue of cold-acclimated Ucp1−/− mice. J Biol Chem 281(42):31894–31908

    Article  PubMed  CAS  Google Scholar 

  • van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360(15):1500–1508

    Article  PubMed  Google Scholar 

  • Vegiopoulos A, Muller-Decker K, Strzoda D, Schmitt I, Chichelnitskiy E, Ostertag A, Berriel DM, Rozman J, de Hrabe AM, Nusing RM, Meyer CW, Wahli W, Klingenspor M, Herzig S (2010) Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328(5982):1158–1161

    Article  PubMed  CAS  Google Scholar 

  • Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerback S, Nuutila P (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360(15):1518–1525

    Article  PubMed  CAS  Google Scholar 

  • Voss-Andreae A, Murphy JG, Ellacott KL, Stuart RC, Nillni EA, Cone RD, Fan W (2007) Role of the central melanocortin circuitry in adaptive thermogenesis of brown adipose tissue. Endocrinology 148(4):1550–1560

    Article  PubMed  CAS  Google Scholar 

  • Watanabe M, Yamamoto T, Mori C, Okada N, Yamazaki N, Kajimoto K, Kataoka M, Shinohara Y (2008) Cold-induced changes in gene expression in brown adipose tissue: implications for the activation of thermogenesis. Biol Pharm Bull 31(5):775–784

    Article  PubMed  CAS  Google Scholar 

  • Winkler E, Klingenberg M (1994) Effect of fatty acids on H  +  transport activity of the reconstituted uncoupling protein. J Biol Chem 269(4):2508–2515

    PubMed  CAS  Google Scholar 

  • Wu Z, Xie Y, Bucher NL, Farmer SR (1995) Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis. Genes Dev 9(19):2350–2363

    Article  PubMed  CAS  Google Scholar 

  • Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98(1):115–124

    Article  PubMed  CAS  Google Scholar 

  • Xue B, Rim JS, 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(1):41–51

    Article  PubMed  CAS  Google Scholar 

  • Zimmermann R, Strauss JG, Haemmerle G, Schoiswohl G, Birner-Gruenberger R, Riederer M, Lass A, Neuberger G, Eisenhaber F, Hermetter A, Zechner R (2004) Fat mobilization in adipose tissue is promoted by adipose triglyceride lipase. Science 306(5700):1383–1386

    Article  PubMed  CAS  Google Scholar 

  • Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, Nedergaard J, Cinti S (2009) The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J 23(9):3113–3120

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors receive financial support from the Else Kröner-Fresenius Stiftung, the German Research Community (Deutsche Forschungsgemeinschaft) and the Federal Ministry for Education and Research (Bundesministerium für Bildung und Forschung).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin Klingenspor .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Klingenspor, M., Fromme, T. (2012). Brown Adipose Tissue. In: Symonds, M. (eds) Adipose Tissue Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-0965-6_3

Download citation

Publish with us

Policies and ethics