Advertisement

Brown Adipose Tissue in Human Infants

  • Martin E. LidellEmail author
Chapter
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

Brown adipose tissue Fetal Human Infant 

Notes

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.

References

  1. Aherne W, Hull D (1966) Brown adipose tissue and heat production in the newborn infant. J Pathol Bacteriol 91:223–234CrossRefGoogle Scholar
  2. 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 297:843–845CrossRefGoogle Scholar
  3. Bonnot E (1908) The interscapular gland. J Anat Physiol 43:43–58PubMedPubMedCentralGoogle Scholar
  4. Brooke OG, Harris M, Salvosa CB (1973) The response of malnourished babies to cold. J Physiol 233:75–91CrossRefGoogle Scholar
  5. Brück K (1961) Temperature regulation in newborn infant. Biol Neonat 3:65–81CrossRefGoogle Scholar
  6. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359CrossRefGoogle Scholar
  7. Cannon B, Nedergaard J (2012) Cell biology: neither brown nor white. Nature 488:286–287CrossRefGoogle Scholar
  8. Cannon B, Hedin A, Nedergaard J (1982) Exclusive occurrence of thermogenin antigen in brown adipose tissue. FEBS Lett 150:129–132CrossRefGoogle Scholar
  9. 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 19:635–639CrossRefGoogle Scholar
  10. Dawkins MJ, Hull D (1965) The production of heat by fat. Sci Am 213:62–67CrossRefGoogle Scholar
  11. Dawkins MJ, Scopes JW (1965) Non-shivering thermogenesis and brown adipose tissue in the human new-born infant. Nature 206:201–202CrossRefGoogle Scholar
  12. 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 108:1379–1385CrossRefGoogle Scholar
  13. 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 34:1679–1691CrossRefGoogle Scholar
  14. Douglas RJ (1992) Could a lowered level of uncoupling protein in brown adipose tissue mitochondria play a role in SIDS aetiology? Med Hypotheses 37:100–102CrossRefGoogle Scholar
  15. Emery JL, Dinsdale F (1978) Structure of periadrenal brown fat in childhood in both expected and cot deaths. Arch Dis Child 53:154–158CrossRefGoogle Scholar
  16. 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 387:90–94CrossRefGoogle Scholar
  17. 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 161:337–339CrossRefGoogle Scholar
  18. Fedorenko A, Lishko PV, Kirichok Y (2012) Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. Cell 151:400–413CrossRefGoogle Scholar
  19. 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 44:1582–1585PubMedGoogle Scholar
  20. 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 34:577–579CrossRefGoogle Scholar
  21. 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 35:984–990CrossRefGoogle Scholar
  22. Grausz JP (1970) Interscapular skin temperatures in the newborn infant. J Pediatr 76:752–756CrossRefGoogle Scholar
  23. Hammar JA (1895) Zur Kenntniss des fettgewebes. Arch Mikrosk Anat 45:512–574CrossRefGoogle Scholar
  24. Harms M, Seale P (2013) Brown and beige fat: development, function and therapeutic potential. Nat Med 19:1252–1263CrossRefGoogle Scholar
  25. 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 21:369–373Google Scholar
  26. Heaton JM (1972) The distribution of brown adipose tissue in the human. J Anat 112:35–39PubMedPubMedCentralGoogle Scholar
  27. 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 82:515–521CrossRefGoogle Scholar
  28. Hey EN (1969) The relation between environmental temperature and oxygen consumption in the new-born baby. J Physiol 200:589–603CrossRefGoogle Scholar
  29. 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 41:759–768CrossRefGoogle Scholar
  30. 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 77:382–387PubMedGoogle Scholar
  31. 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 35:938–942CrossRefGoogle Scholar
  32. 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 38:885–896CrossRefGoogle Scholar
  33. 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 32:107–117CrossRefGoogle Scholar
  34. Karlberg P, Moore RE, Oliver TK Jr (1962) The thermogenic response of the newborn infant to noradrenaline. Acta Paediatr 51:284–292CrossRefGoogle Scholar
  35. Kinney HC, Thach BT (2009) The sudden infant death syndrome. N Engl J Med 361:795–805CrossRefGoogle Scholar
  36. Kooijman S, van den Heuvel JK, Rensen PC (2015) Neuronal control of brown fat activity. Trends Endocrinol Metab 26:657–668CrossRefGoogle Scholar
  37. 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 41:759–764CrossRefGoogle Scholar
  38. Lean ME, James WP (1983) Uncoupling protein in human brown adipose tissue mitochondria. Isolation and detection by specific antiserum. FEBS Lett 163:235–240CrossRefGoogle Scholar
  39. Lean ME, Jennings G (1989) Brown adipose tissue activity in pyrexial cases of cot death. J Clin Pathol 42:1153–1156CrossRefGoogle Scholar
  40. Lean ME, James WP, Jennings G, Trayhurn P (1986) Brown adipose tissue uncoupling protein content in human infants, children and adults. Clin Sci (Lond) 71:291–297CrossRefGoogle Scholar
  41. 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 19:631–634CrossRefGoogle Scholar
  42. Lidell ME, Betz MJ, Enerbäck S (2014) Brown adipose tissue and its therapeutic potential. J Intern Med 276:364–377CrossRefGoogle Scholar
  43. Lin CS, Klingenberg M (1980) Isolation of the uncoupling protein from brown adipose tissue mitochondria. FEBS Lett 113:299–303CrossRefGoogle Scholar
  44. 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 19:810–820CrossRefGoogle Scholar
  45. 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 366:740–742CrossRefGoogle Scholar
  46. Merklin RJ (1974) Growth and distribution of human fetal brown fat. Anat Rec 178:637–645CrossRefGoogle Scholar
  47. Oelkrug R, Polymeropoulos ET, Jastroch M (2015) Brown adipose tissue: physiological function and evolutionary significance. J Comp Physiol B 185:587–606CrossRefGoogle Scholar
  48. 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 43:1234–1240PubMedGoogle Scholar
  49. 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 44:1421–1425PubMedGoogle Scholar
  50. 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 14:272–279CrossRefGoogle Scholar
  51. Rasmussen AT (1923) The so-called hibernating gland. J Morphol 38:147–205CrossRefGoogle Scholar
  52. Ricquier D, Kader JC (1976) Mitochondrial protein alteration in active brown fat: a soidum dodecyl sulfate-polyacrylamide gel electrophoretic study. Biochem Biophys Res Commun 73:577–583CrossRefGoogle Scholar
  53. Rylander E, Pribylova H, Lind J (1972) A thermographic study of infants exposed to cold. Acta Paediatr Scand 61:42–48CrossRefGoogle Scholar
  54. Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M (2016) Imaging of brown adipose tissue: state of the art. Radiology 280:4–19CrossRefGoogle Scholar
  55. Sawczenko A, Fleming PJ (1996) Thermal stress, sleeping position, and the sudden infant death syndrome. Sleep 19:S267–S270PubMedGoogle Scholar
  56. 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 454:961–967CrossRefGoogle Scholar
  57. 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:e49452CrossRefGoogle Scholar
  58. Shattock SG (1909) On normal tumour-like formations of fat in man and the lower animals. Proc R Soc Med 2:207–270PubMedPubMedCentralGoogle Scholar
  59. Shaw HB (1901) A contribution to the study of the morphology of adipose tissue. J Anat Physiol 36:1–13PubMedPubMedCentralGoogle Scholar
  60. Sheldon EF (1924) The so-called hibernating gland in mammals: a form of adipose tissue. Anat Rec 28:331–347CrossRefGoogle Scholar
  61. Silva JE (2006) Thermogenic mechanisms and their hormonal regulation. Physiol Rev 86:435–464CrossRefGoogle Scholar
  62. Silverman WA, Zamelis A, Sinclair JC, Agate FJ (1964) Warm nap of the newborn. Pediatrics 33:984–987PubMedGoogle Scholar
  63. Smith RE, Horwitz BA (1969) Brown fat and thermogenesis. Physiol Rev 49:330–425CrossRefGoogle Scholar
  64. Thomas SA, Palmiter RD (1997) Thermoregulatory and metabolic phenotypes of mice lacking noradrenaline and adrenaline. Nature 387:94–97CrossRefGoogle Scholar
  65. 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 99:151–159CrossRefGoogle Scholar
  66. 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 23:350–359CrossRefGoogle Scholar
  67. 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 150:366–376CrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Medical Biochemistry and Cell BiologyInstitute of Biomedicine, The Sahlgrenska Academy, University of GothenburgGothenburgSweden

Personalised recommendations