Skip to main content

Brown Adipose Tissue in Human Infants

Part of the Handbook of Experimental Pharmacology book series (HEP,volume 251)

Abstract

Adapting to the cold extrauterine environment after birth is a great challenge for the newborn. Due to their high surface area-to-volume ratio, infants tend to lose more heat to the environment as compared to adults. In addition, human newborns lack sufficiently developed skeletal muscle mass to maintain body temperature through shivering thermogenesis, an important source of heat in cold-exposed adults. Evolution has provided humans and other placental mammals with brown adipose tissue (BAT), a tissue that converts chemically stored energy, in the form of fatty acids and glucose, into heat through non-shivering thermogenesis. The thermogenic activity of this tissue is significant for the human infant’s ability to maintain a sufficiently high core body temperature. Although BAT has been studied in human infants for more than a century, the literature covering different aspects of the tissue is rather limited. The aim of this review is to summarize the literature and describe what is actually known about the tissue and its importance for early human life.

Keywords

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

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD   219.99
Price excludes VAT (USA)
  • Durable hardcover 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

Learn about institutional subscriptions

References

  • Aherne W, Hull D (1966) Brown adipose tissue and heat production in the newborn infant. J Pathol Bacteriol 91:223–234

    Article  CAS  Google Scholar 

  • Bachman ES, Dhillon H, Zhang CY, Cinti S, Bianco AC, Kobilka BK, Lowell BB (2002) betaAR signaling required for diet-induced thermogenesis and obesity resistance. Science 297:843–845

    Article  CAS  Google Scholar 

  • Bonnot E (1908) The interscapular gland. J Anat Physiol 43:43–58

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brooke OG, Harris M, Salvosa CB (1973) The response of malnourished babies to cold. J Physiol 233:75–91

    Article  CAS  Google Scholar 

  • Brück K (1961) Temperature regulation in newborn infant. Biol Neonat 3:65–81

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Cannon B, Nedergaard J (2012) Cell biology: neither brown nor white. Nature 488:286–287

    Article  CAS  Google Scholar 

  • Cannon B, Hedin A, Nedergaard J (1982) Exclusive occurrence of thermogenin antigen in brown adipose tissue. FEBS Lett 150:129–132

    Article  CAS  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 19:635–639

    Article  CAS  Google Scholar 

  • Dawkins MJ, Hull D (1965) The production of heat by fat. Sci Am 213:62–67

    Article  CAS  Google Scholar 

  • Dawkins MJ, Scopes JW (1965) Non-shivering thermogenesis and brown adipose tissue in the human new-born infant. Nature 206:201–202

    Article  CAS  Google Scholar 

  • de Jesus LA, Carvalho SD, Ribeiro MO, Schneider M, Kim SW, Harney JW, Larsen PR, Bianco AC (2001) The type 2 iodothyronine deiodinase is essential for adaptive thermogenesis in brown adipose tissue. J Clin Invest 108:1379–1385

    Article  Google Scholar 

  • Di Franco A, Guasti D, Squecco R, Mazzanti B, Rossi F, Idrizaj E, Gallego-Escuredo JM, Villarroya F, Bani D, Forti G, Vannelli GB, Luconi M (2016) Searching for classical brown fat in humans: development of a novel human fetal brown stem cell model. Stem Cells 34:1679–1691

    Article  Google Scholar 

  • Douglas RJ (1992) Could a lowered level of uncoupling protein in brown adipose tissue mitochondria play a role in SIDS aetiology? Med Hypotheses 37:100–102

    Article  CAS  Google Scholar 

  • Emery JL, Dinsdale F (1978) Structure of periadrenal brown fat in childhood in both expected and cot deaths. Arch Dis Child 53:154–158

    Article  CAS  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

    Article  Google Scholar 

  • Fatemi A, Item C, Stockler-Ipsiroglu S, Ipsiroglu O, Sperl W, Patsch W, Strobl W (2002) Sudden infant death: no evidence for linkage to common polymorphisms in the uncoupling protein-1 and the beta3-adrenergic receptor genes. Eur J Pediatr 161:337–339

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Fukuchi K, Ono Y, Nakahata Y, Okada Y, Hayashida K, Ishida Y (2003) Visualization of interscapular brown adipose tissue using (99 m)Tc-tetrofosmin in pediatric patients. J Nucl Med 44:1582–1585

    PubMed  Google Scholar 

  • Gelfand MJ (2004) 123I-MIBG uptake in the neck and shoulders of a neuroblastoma patient: damage to sympathetic innervation blocks uptake in brown adipose tissue. Pediatr Radiol 34:577–579

    Article  Google Scholar 

  • Gelfand MJ, O'Hara SM, Curtwright LA, Maclean JR (2005) Pre-medication to block [(18)F]FDG uptake in the brown adipose tissue of pediatric and adolescent patients. Pediatr Radiol 35:984–990

    Article  Google Scholar 

  • Grausz JP (1970) Interscapular skin temperatures in the newborn infant. J Pediatr 76:752–756

    Article  CAS  Google Scholar 

  • Hammar JA (1895) Zur Kenntniss des fettgewebes. Arch Mikrosk Anat 45:512–574

    Article  Google Scholar 

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

    Article  CAS  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. Anat Anz 21:369–373

    Google Scholar 

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

    CAS  PubMed  PubMed Central  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 82:515–521

    Article  CAS  Google Scholar 

  • Hey EN (1969) The relation between environmental temperature and oxygen consumption in the new-born baby. J Physiol 200:589–603

    Article  CAS  Google Scholar 

  • Hong TS, Shammas A, Charron M, Zukotynski KA, Drubach LA, Lim R (2011) Brown adipose tissue 18F-FDG uptake in pediatric PET/CT imaging. Pediatr Radiol 41:759–768

    Article  Google Scholar 

  • Houstek J, Vizek K, Pavelka S, Kopecky J, Krejcova E, Hermanska J, Cermakova M (1993) Type II iodothyronine 5′-deiodinase and uncoupling protein in brown adipose tissue of human newborns. J Clin Endocrinol Metab 77:382–387

    CAS  PubMed  Google Scholar 

  • Hu HH, Tovar JP, Pavlova Z, Smith ML, Gilsanz V (2012) Unequivocal identification of brown adipose tissue in a human infant. J Magn Reson Imaging 35:938–942

    Article  Google Scholar 

  • Hu HH, Yin L, Aggabao PC, Perkins TG, Chia JM, Gilsanz V (2013) Comparison of brown and white adipose tissues in infants and children with chemical-shift-encoded water-fat MRI. J Magn Reson Imaging 38:885–896

    Article  Google Scholar 

  • Hu HH, Wu TW, Yin L, Kim MS, Chia JM, Perkins TG, Gilsanz V (2014) MRI detection of brown adipose tissue with low fat content in newborns with hypothermia. Magn Reson Imaging 32:107–117

    Article  Google Scholar 

  • Karlberg P, Moore RE, Oliver TK Jr (1962) The thermogenic response of the newborn infant to noradrenaline. Acta Paediatr 51:284–292

    Article  CAS  Google Scholar 

  • Kinney HC, Thach BT (2009) The sudden infant death syndrome. N Engl J Med 361:795–805

    Article  CAS  Google Scholar 

  • Kooijman S, van den Heuvel JK, Rensen PC (2015) Neuronal control of brown fat activity. Trends Endocrinol Metab 26:657–668

    Article  CAS  Google Scholar 

  • Kortelainen ML, Pelletier G, Ricquier D, Bukowiecki LJ (1993) Immunohistochemical detection of human brown adipose tissue uncoupling protein in an autopsy series. J Histochem Cytochem 41:759–764

    Article  CAS  Google Scholar 

  • Lean ME, James WP (1983) Uncoupling protein in human brown adipose tissue mitochondria. Isolation and detection by specific antiserum. FEBS Lett 163:235–240

    Article  CAS  Google Scholar 

  • Lean ME, Jennings G (1989) Brown adipose tissue activity in pyrexial cases of cot death. J Clin Pathol 42:1153–1156

    Article  CAS  Google Scholar 

  • Lean ME, James WP, Jennings G, Trayhurn P (1986) Brown adipose tissue uncoupling protein content in human infants, children and adults. Clin Sci (Lond) 71:291–297

    Article  CAS  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

    Article  CAS  Google Scholar 

  • Lidell ME, Betz MJ, Enerbäck S (2014) Brown adipose tissue and its therapeutic potential. J Intern Med 276:364–377

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC, Kong X, Rao RR, Lou J, Lokurkar I, Baur W, Castellot JJ Jr, Rosen ED, Spiegelman BM (2014) A smooth muscle-like origin for beige adipocytes. Cell Metab 19:810–820

    Article  CAS  Google Scholar 

  • Lowell BB, SS V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP, Flier JS (1993) Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature 366:740–742

    Article  CAS  Google Scholar 

  • Merklin RJ (1974) Growth and distribution of human fetal brown fat. Anat Rec 178:637–645

    Article  CAS  Google Scholar 

  • Oelkrug R, Polymeropoulos ET, Jastroch M (2015) Brown adipose tissue: physiological function and evolutionary significance. J Comp Physiol B 185:587–606

    Article  CAS  Google Scholar 

  • Okuyama C, Sakane N, Yoshida T, Shima K, Kurosawa H, Kumamoto K, Ushijima Y, Nishimura T (2002) (123)I- or (125)I-metaiodobenzylguanidine visualization of brown adipose tissue. J Nucl Med 43:1234–1240

    CAS  PubMed  Google Scholar 

  • Okuyama C, Ushijima Y, Kubota T, Yoshida T, Nakai T, Kobayashi K, Nishimura T (2003) 123I-Metaiodobenzylguanidine uptake in the nape of the neck of children: likely visualization of brown adipose tissue. J Nucl Med 44:1421–1425

    CAS  PubMed  Google Scholar 

  • Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, Scheinin M, Taittonen M, Niemi T, Enerbäck S, Virtanen KA (2011) Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 14:272–279

    Article  CAS  Google Scholar 

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

    Article  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 73:577–583

    Article  CAS  Google Scholar 

  • Rylander E, Pribylova H, Lind J (1972) A thermographic study of infants exposed to cold. Acta Paediatr Scand 61:42–48

    Article  CAS  Google Scholar 

  • Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M (2016) Imaging of brown adipose tissue: state of the art. Radiology 280:4–19

    Article  Google Scholar 

  • Sawczenko A, Fleming PJ (1996) Thermal stress, sleeping position, and the sudden infant death syndrome. Sleep 19:S267–S270

    CAS  PubMed  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 454:961–967

    Article  CAS  Google Scholar 

  • Sharp LZ, Shinoda K, Ohno H, Scheel DW, Tomoda E, Ruiz L, Hu H, Wang L, Pavlova Z, Gilsanz V, Kajimura S (2012) Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS One 7:e49452

    Article  CAS  Google Scholar 

  • Shattock SG (1909) On normal tumour-like formations of fat in man and the lower animals. Proc R Soc Med 2:207–270

    CAS  PubMed  PubMed Central  Google Scholar 

  • Shaw HB (1901) A contribution to the study of the morphology of adipose tissue. J Anat Physiol 36:1–13

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sheldon EF (1924) The so-called hibernating gland in mammals: a form of adipose tissue. Anat Rec 28:331–347

    Article  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Silverman WA, Zamelis A, Sinclair JC, Agate FJ (1964) Warm nap of the newborn. Pediatrics 33:984–987

    CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  • Thomas SA, Palmiter RD (1997) Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387:94–97

    Article  CAS  Google Scholar 

  • Velickovic K, Cvoro A, Srdic B, Stokic E, Markelic M, Golic I, Otasevic V, Stancic A, Jankovic A, Vucetic M, Buzadzic B, Korac B, Korac A (2014) Expression and subcellular localization of estrogen receptors alpha and beta in human fetal brown adipose tissue. J Clin Endocrinol Metab 99:151–159

    Article  CAS  Google Scholar 

  • Vishvanath L, MacPherson KA, Hepler C, Wang QA, Shao M, Spurgin SB, Wang MY, Kusminski CM, Morley TS, Gupta RK (2016) Pdgfrbeta+ mural preadipocytes contribute to adipocyte hyperplasia induced by high-fat-diet feeding and prolonged cold exposure in adult mice. Cell Metab 23:350–359

    Article  CAS  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

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author is supported by the Swedish Research Council, Wilhelm and Martina Lundgren’s Foundation, and The Royal Society of Arts and Sciences in Gothenburg.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Martin E. Lidell .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lidell, M.E. (2018). Brown Adipose Tissue in Human Infants. In: Pfeifer, A., Klingenspor, M., Herzig, S. (eds) Brown Adipose Tissue. Handbook of Experimental Pharmacology, vol 251. Springer, Cham. https://doi.org/10.1007/164_2018_118

Download citation

Publish with us

Policies and ethics