Skip to main content

Brown Adipose Tissue and Body Weight Regulation

  • Chapter
  • First Online:
Pediatric Obesity

Part of the book series: Contemporary Endocrinology ((COE))

Abstract

Brown adipose tissue plays a critical role in neonatal thermogenesis, insuring survival of the newborn infant during the transition from intrauterine to extrauterine life. In rodents, the generation and/or expansion of brown adipose tissue within white adipose depots (“beiging”) provides a defense against obesity and glucose intolerance. Here we describe the origin and development of brown adipocytes, the hormonal control of “beiging” in humans and other mammals, the effects of obesity on brown adipose mass and activity, and the implications of brown adipose for human metabolic homeostasis.

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

Access this chapter

Institutional subscriptions

References

  1. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293:E444–52.

    Article  CAS  PubMed  Google Scholar 

  2. 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. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58(7):1526–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Au-Yong IT, Thorn N, Ganatra R, Perkins AC, Symonds ME. Brown adipose tissue and seasonal variation in humans. Diabetes. 2009;58(11):2583–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, Taittonen M, Laine J, Savisto NJ, Enerbäck S, Nuutila P. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360(15):1518–25.

    Article  CAS  PubMed  Google Scholar 

  5. van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360(15):1500–8.

    Article  PubMed  Google Scholar 

  6. Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Pfannenberg C, Werner MK, Ripkens S, Stef I, Deckert A, Schmadl M, Reimold M, Häring HU, Claussen CD, Stefan N. Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes. 2010;59(7):1789–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Lowell BB, S-Susulic V, Hamann A, Lawitts JA, Himms-Hagen J, Boyer BB, Kozak LP, Flier JS. Development of obesity in transgenic mice after genetic ablation of brown adipose tissue. Nature. 1993;366(6457):740–2.

    Article  CAS  PubMed  Google Scholar 

  9. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009;9(2):203–9.

    Article  CAS  PubMed  Google Scholar 

  10. Cohen P, Levy JD, Zhang Y, Frontini A, Kolodin DP, Svensson KJ, Lo JC, Zeng X, Ye L, Khandekar MJ, Wu J, Gunawardana SC, Banks AS, Camporez JP, Jurczak MJ, Kajimura S, Piston DW, Mathis D, Cinti S, Shulman GI, Seale P, Spiegelman BM. Ablation of PRDM16 and beige adipose causes metabolic dysfunction and a subcutaneous to visceral fat switch. Cell. 2014;156(1-2):304–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Cederberg A, Grønning LM, Ahrén B, Taskén K, Carlsson P, Enerbäck S. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell. 2001;106(5):563–73.

    Article  CAS  PubMed  Google Scholar 

  12. 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. A smooth muscle-like origin for beige adipocytes. Cell Metab. 2014;19(5):810–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Wang W, Seale P. Control of brown and beige fat development. Nat Rev Mol Cell Biol. 2016;17(11):691–702.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Giordano A, Smorlesi A, Frontini A, Barbatelli G, Cinti S. White, brown and pink adipocytes: the extraordinary plasticity of the adipose organ. Eur J Endocrinol. 2014;170(5):R159–71.

    Article  CAS  PubMed  Google Scholar 

  15. Collins S, Daniel KW, Petro AE, Surwit RS. Strain-specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice. Endocrinology. 1997;138(1):405–13.

    Article  CAS  PubMed  Google Scholar 

  16. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest. 1998;102(2):412–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Pope M, Budge H, Symonds ME. The developmental transition of ovine adipose tissue through early life. Acta Physiol (Oxf). 2014;210(1):20–30.

    Article  CAS  Google Scholar 

  18. Hall JA, Ribich S, Christoffolete MA, Simovic G, Correa-Medina M, Patti ME, Bianco AC. Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology. 2010;151(9):4573–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Oden J, Fleenor D, Driscoll P, Freemark M. Leptin in the newborn mouse. Plasma concentrations, characterization of the circulating hormone, and tissue source. Biol Neonate. 2002;82(2):109–16.

    Article  CAS  PubMed  Google Scholar 

  20. Emery JL, Dinsdale F. Structure of periadrenal brown fat in childhood in both expected and cot deaths. Arch Dis Child. 1978;53(2):154–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lean ME, James WP, Jennings G, Trayhurn P. Brown adipose tissue uncoupling protein content in human infants, children and adults. Clin Sci (Lond). 1986;71(3):291–7.

    Article  CAS  Google Scholar 

  22. Merklin RJ. Growth and distribution of human fetal brown fat. Anat Rec. 1974;178(3):637–45.

    Article  CAS  PubMed  Google Scholar 

  23. Houstĕk J, Vízek K, Pavelka S, Kopecký J, Krejcová E, Hermanská J, Cermáková M. Type II iodothyronine 5′-deiodinase and uncoupling protein in brown adipose tissue of human newborns. J Clin Endocrinol Metab. 1993;77(2):382–7.

    PubMed  Google Scholar 

  24. Gilsanz V, Smith ML, Goodarzian F, Kim M, Wren TA, Hu HH. Changes in brown adipose tissue in boys and girls during childhood and puberty. J Pediatr. 2012;160(4):604–9.

    Article  PubMed  Google Scholar 

  25. Drubach LA, Palmer EL 3rd, Connolly LP, Baker A, Zurakowski D, Cypess AM. Pediatric brown adipose tissue: detection, epidemiology, and differences from adults. J Pediatr. 2011;159(6):939–44.

    Article  CAS  PubMed  Google Scholar 

  26. Tseng YH, Kriauciunas KM, Kokkotou E, Kahn CR. Differential roles of insulin receptor substrates in brown adipocyte differentiation. Mol Cell Biol. 2004;24(5):1918–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Cypess AM, Zhang H, Schulz TJ, Huang TL, Espinoza DO, Kristiansen K, Unterman TG, Tseng YH. Insulin/IGF-I regulation of necdin and brown adipocyte differentiation via CREB- and FoxO1-associated pathways. Endocrinology. 2011;152(10):3680–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Boucher J, Softic S, El Ouaamari A, Krumpoch MT, Kleinridders A, Kulkarni RN, O'Neill BT, Kahn CR. Differential roles of insulin and IGF-1 receptors in adipose tissue development and function. Diabetes. 2016;65(8):2201–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Smith DW, Klein AM, Henderson JR, Myrianthopoulos NC. Congenital hypothyroidism--signs and symptoms in the newborn period. J Pediatr. 1975;87(6 Pt 1):958–62.

    Article  CAS  PubMed  Google Scholar 

  30. Schermer SJ, Bird JA, Lomax MA, Shepherd DA, Symonds ME. Effect of fetal thyroidectomy on brown adipose tissue and thermoregulation in newborn lambs. Reprod Fertil Dev. 1996;8(6):995–1002.

    Article  CAS  PubMed  Google Scholar 

  31. Mostyn A, Pearce S, Budge H, Elmes M, Forhead AJ, Fowden AL, Stephenson T, Symonds ME. Influence of cortisol on adipose tissue development in the fetal sheep during late gestation. J Endocrinol. 2003;176(1):23–30.

    Article  CAS  PubMed  Google Scholar 

  32. Forhead AJ, Curtis K, Kaptein E, Visser TJ, Fowden AL. Developmental control of iodothyronine deiodinases by cortisol in the ovine fetus and placenta near term. Endocrinology. 2006;147(12):5988–94.

    Article  CAS  PubMed  Google Scholar 

  33. Moriscot A, Rabelo R, Bianco AC. Corticosterone inhibits uncoupling protein gene expression in brown adipose tissue. Am J Phys. 1993;265(1 Pt 1):E81–7.

    CAS  Google Scholar 

  34. Collins S, Bolanowski MA, Caron MG, Lefkowitz RJ. Genetic regulation of beta-adrenergic receptors. Annu Rev Physiol. 1989;51:203–15.

    Article  CAS  PubMed  Google Scholar 

  35. Fève B, Emorine LJ, Briend-Sutren MM, Lasnier F, Strosberg AD, Pairault J. Differential regulation of beta 1- and beta 2-adrenergic receptor protein and mRNA levels by glucocorticoids during 3T3-F442A adipose differentiation. J Biol Chem. 1990;265(27):16343–9.

    PubMed  Google Scholar 

  36. Kratzsch J, Schubring C, Stitzel B, Böttner A, Berthold A, Thiery J, Kiess W. Inverse changes in the serum levels of the soluble leptin receptor and leptin in neonates: relations to anthropometric data. J Clin Endocrinol Metab. 2005;90(4):2212–7.

    Article  CAS  PubMed  Google Scholar 

  37. Yuen BS, Owens PC, Muhlha¨usler BS, Roberts CT, Symonds ME, Keisler DH, McFarlane JR, Kauter KG, Evens Y, McMillen IC. Leptin alters the structural and functional characteristics of adipose tissue before birth. FASEB J. 2003;17:1102–4.

    CAS  PubMed  Google Scholar 

  38. Commins SP, Marsh DJ, Thomas SA, Watson PM, Padgett MA, Palmiter R, Gettys TW. Norepinephrine is required for leptin effects on gene expression in brown and white adipose tissue. Endocrinology. 1999;140(10):4772–8.

    Article  CAS  PubMed  Google Scholar 

  39. Mistry AM, Swick A, Romsos DR. Leptin alters metabolic rates before acquisition of its anorectic effect in developing neonatal mice. Am J Phys. 1999;277(3 Pt 2):R742–7.

    CAS  Google Scholar 

  40. Royster M, Driscoll P, Kelly PA, Freemark M. The prolactin receptor in the fetal rat: cellular localization of messenger ribonucleic acid, immunoreactive protein, and ligand-binding activity and induction of expression in late gestation. Endocrinology. 1995;136(9):3892–900.

    Article  CAS  PubMed  Google Scholar 

  41. Pearce S, Budge H, Mostyn A, Genever E, Webb R, Ingleton P, Walker AM, Symonds ME, Stephenson T. Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep. J Endocrinol. 2005;184(2):351–9.

    Article  CAS  PubMed  Google Scholar 

  42. Viengchareun S, Servel N, Fève B, Freemark M, Lombès M, Binart N. Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2. PLoS One. 2008;3(2):e1535.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Auffret J, Viengchareun S, Carré N, Denis RG, Magnan C, Marie PY, Muscat A, Fève B, Lombès M, Binart N. Beige differentiation of adipose depots in mice lacking prolactin receptor protects against high-fat-diet-induced obesity. FASEB J. 2012;26(9):3728–37.

    Article  CAS  PubMed  Google Scholar 

  44. Li Y, Knapp JR, Kopchick JJ. Interscapular brown adipose tissue in growth hormone antagonist and in growth hormone receptor gene-disrupted dwarf mice. Exp Biol Med. 2003;228:207–15.

    Article  CAS  Google Scholar 

  45. Kooijman S, van den Heuvel JK, Rensen PC. Neuronal control of Brown fat activity. Trends Endocrinol Metab. 2015;26(11):657–68.

    Article  CAS  PubMed  Google Scholar 

  46. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84:277e359.

    Article  Google Scholar 

  47. Morak M, Schmidinger H, Riesenhuber G, Rechberger GN, Kollroser M, Haemmerle G, Zechner R, Kronenberg F, Hermetter A. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues. Mol Cell Proteomics. 2012;11(12):1777–89.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Ribeiro MO, Lebrun FL, Christoffolete MA, Branco M, Crescenzi A, Carvalho SD, Negrão N, Bianco AC. Evidence of UCP1-independent regulation of norepinephrine-induced thermogenesis in brown fat. Am J Physiol Endocrinol Metab. 2000;279(2):E314–22.

    Article  CAS  PubMed  Google Scholar 

  49. Pelletier P, Gauthier K, Sideleva O, Samarut J, Silva JE. Mice lacking the thyroid hormone receptor-alpha gene spend more energy in thermogenesis, burn more fat, and are less sensitive to high-fat diet-induced obesity. Endocrinology. 2008;149(12):6471–86.

    Article  CAS  PubMed  Google Scholar 

  50. Ribeiro MO, Bianco SD, Kaneshige M, Schultz JJ, Cheng SY, Bianco AC, Brent GA. Expression of uncoupling protein 1 in mouse brown adipose tissue is thyroid hormone receptor-beta isoform specific and required for adaptive thermogenesis. Endocrinology. 2010;151(1):432–40.

    Article  CAS  PubMed  Google Scholar 

  51. Collins S, Cao W, Robidoux J. Learning new tricks from old dogs: beta-adrenergic receptors teach new lessons on firing up adipose tissue metabolism. Mol Endocrinol. 2004;18(9):2123–31. 28

    Article  CAS  PubMed  Google Scholar 

  52. Iida S, Chen W, Nakadai T, Ohkuma Y, Roeder RG. PRDM16 enhances nuclear receptor dependent transcription of the brown fat-specific Ucp1 gene through interactions with mediator subunit MED1. Genes Dev. 2014;29:308–21.

    Article  CAS  Google Scholar 

  53. Guerra C, Porras A, Roncero C, Benito M, Fernandez M. Triiodothyronine induces the expression of the uncoupling protein in long term fetal rat brown adipocyte primary cultures: role of nuclear thyroid hormone receptor expression. Endocrinology. 1994;134(3):1067–74.

    Article  CAS  PubMed  Google Scholar 

  54. Guerra C, Roncero C, Porras A, Fernández M, Benito M. Triiodothyronine induces the transcription of the uncoupling protein gene and stabilizes its mRNA in fetal rat brown adipocyte primary cultures. J Biol Chem. 1996;271(4):2076–81.

    Article  CAS  PubMed  Google Scholar 

  55. López M, Varela L, Vázquez MJ, Rodríguez-Cuenca S, González CR, Velagapudi VR, Morgan DA, Schoenmakers E, Agassandian K, Lage R, Martínez de Morentin PB, Tovar S, Nogueiras R, Carling D, Lelliott C, Gallego R, Oresic M, Chatterjee K, Saha AK, Rahmouni K, Diéguez C, Vidal-Puig A. Hypothalamic AMPK and fatty acid metabolism mediate thyroid regulation of energy balance. Nat Med. 2010;16(9):1001–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Martínez-Sánchez N, Alvarez CV, Fernø J, Nogueiras R, Diéguez C, López M. Hypothalamic effects of thyroid hormones on metabolism. Best Pract Res Clin Endocrinol Metab. 2014;28(5):703–12.

    Article  PubMed  CAS  Google Scholar 

  57. Alvarez-Crespo M, Csikasz RI, Martínez-Sánchez N, Diéguez C, Cannon B, Nedergaard J, López M. Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance. Mol Metab. 2016;5(4):271–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rockstroh D, Landgraf K, Wagner IV, Gesing J, Tauscher R, Lakowa N, Kiess W, Bühligen U, Wojan M, Till H, Blüher M, Körner A. Direct evidence of brown adipocytes in different fat depots in children. PLoS One. 2015;10(2):e0117841.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  59. Cypess AM, Haft CR, Laughlin MR, Hu HH. Brown fat in humans: consensus points and experimental guidelines. Cell Metab. 2014;20(3):408–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, Schaart G, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD. Short-term cold acclimation recruits Brown adipose tissue in obese humans. Diabetes. 2016;65(5):1179–89.

    Article  CAS  PubMed  Google Scholar 

  61. Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elía E, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, Kolodny GM. Activation of human brown adipose tissue by a β3-adrenergic receptor agonist. Cell Metab. 2015;21(1):33–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Hanssen MJ, Broeders E, Samms RJ, Vosselman MJ, van der Lans AA, Cheng CC, Adams AC, van Marken Lichtenbelt WD, Schrauwen P. Serum FGF21 levels are associated with brown adipose tissue activity in humans. Sci Rep. 2015;5:10275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Lee P, Werner CD, Kebebew E, Celi FS. Functional thermogenic beige adipogenesis is inducible in human neck fat. Int J Obes. 2014;38(2):170–6.

    Article  CAS  Google Scholar 

  64. Douris N, Stevanovic DM, Fisher FM, Cisu TI, Chee MJ, Nguyen NL, Zarebidaki E, Adams AC, Kharitonenkov A, Flier JS, Bartness TJ, Maratos-Flier E. Central fibroblast growth factor 21 browns white fat via sympathetic action in male mice. Endocrinology. 2015;156(7):2470–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kim KH, Lee MS. FGF21 as a stress hormone: the roles of FGF21 in stress adaptation and the treatment of metabolic diseases. Diabetes Metab J. 2014;38(4):245–51.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F. Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem. 2011;286(15):12983–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Bunt JC. Hormonal alterations due to exercise. Sports Med. 1986;3(5):331–45.

    Article  CAS  PubMed  Google Scholar 

  68. Moro C, Crampes F, Sengenes C, De Glisezinski I, Galitzky J, Thalamas C, Lafontan M, Berlan M. Atrial natriuretic peptide contributes to physiological control of lipid mobilization in humans. FASEB J. 2004;18(7):908–10.

    CAS  PubMed  Google Scholar 

  69. Collins S. A heart-adipose tissue connection in the regulation of energy metabolism. Nat Rev Endocrinol. 2014;10(3):157–63.

    Article  CAS  PubMed  Google Scholar 

  70. Bordicchia M, Liu D, Amri EZ, Ailhaud G, Dessì-Fulgheri P, Zhang C, Takahashi N, Sarzani R, Collins S. Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest. 2012;122(3):1022–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Wang TJ, Larson MG, Levy D, Benjamin EJ, Leip EP, Wilson PW, Vasan RS. Impact of obesity on plasma natriuretic peptide levels. Circulation. 2004;109(5):594–600.

    Article  CAS  PubMed  Google Scholar 

  72. Rydén M, Bäckdahl J, Petrus P, Thorell A, Gao H, Coue M, Langin D, Moro C, Arner P. Impaired atrial natriuretic peptide-mediated lipolysis in obesity. Int J Obes. 2016;40(4):714–20.

    Article  CAS  Google Scholar 

  73. Morton NM, Nelson YB, Michailidou Z, Di Rollo EM, Ramage L, Hadoke PW, Seckl JR, Bunger L, Horvat S, Kenyon CJ, Dunbar DR. A stratified transcriptomics analysis of polygenic fat and lean mouse adipose tissues identifies novel candidate obesity genes. PLoS One. 2011;6(9):e23944.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Kovacova Z, Tharp WG, Liu D, Wei W, Xie H, Collins S, Pratley RE. Adipose tissue natriuretic peptide receptor expression is related to insulin sensitivity in obesity and diabetes. Obesity (Silver Spring). 2016;24(4):820–8.

    Article  CAS  Google Scholar 

  75. Reihmane D, Jurka A, Tretjakovs P, Dela F. Increase in IL-6, TNF-α, and MMP-9, but not sICAM-1, concentrations depends on exercise duration. Eur J Appl Physiol. 2013;113(4):851–8.

    Article  CAS  PubMed  Google Scholar 

  76. Ma Y, Gao M, Sun H, Liu D. Interleukin-6 gene transfer reverses body weight gain and fatty liver in obese mice. Biochim Biophys Acta. 2015;1852(5):1001–11.

    Article  CAS  PubMed  Google Scholar 

  77. Kelly AS, Ryder JR, Marlatt KL, Rudser KD, Jenkins T, Inge TH. Changes in inflammation, oxidative stress and adipokines following bariatric surgery among adolescents with severe obesity. Int J Obes. 2016;40(2):275–80.

    Article  CAS  Google Scholar 

  78. De Filippo G, Rendina D, Moccia F, Rocco V, Campanozzi A. Interleukin-6, soluble interleukin-6 receptor/interleukin-6 complex and insulin resistance in obese children and adolescents. J Endocrinol Investig. 2015;38(3):339–43.

    Article  CAS  Google Scholar 

  79. Lee P, Linderman JD, Smith S, Brychta RJ, Wang J, Idelson C, Perron RM, Werner CD, Phan GQ, Kammula US, Kebebew E, Pacak K, Chen KY, Celi FS. Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab. 2014;19(2):302–9.

    Article  CAS  PubMed  Google Scholar 

  80. Zhang Y, Li R, Meng Y, Li S, Donelan W, Zhao Y, Qi L, Zhang M, Wang X, Cui T, Yang LJ, Tang D. Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling. Diabetes. 2014;63(2):514–25.

    Article  CAS  PubMed  Google Scholar 

  81. Palacios-González B, Vadillo-Ortega F, Polo-Oteyza E, Sánchez T, Ancira-Moreno M, Romero-Hidalgo S, Meráz N, Antuna-Puente B. Irisin levels before and after physical activity among school-age children with different BMI: a direct relation with leptin. Obesity (Silver Spring). 2015;23(4):729–32.

    Article  CAS  Google Scholar 

  82. Crujeiras AB, Pardo M, Casanueva FF. Irisin: ‘fat’ or artefact. Clin Endocrinol. 2015;82(4):467–74.

    Article  CAS  Google Scholar 

  83. Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, Lee S, Brenmoehl J, Thomas S, Drevon CA, Erickson HP, Maak S. Irisin - a myth rather than an exercise-inducible myokine. Sci Rep. 2015;5:8889.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J. Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. Nature. 2006;439:484–9.

    Article  CAS  PubMed  Google Scholar 

  85. Fang S, Suh JM, Reilly SM, Yu E, Osborn O, Lackey D, Yoshihara E, Perino A, Jacinto S, Lukasheva Y, Atkins AR, Khvat A, Schnabl B, Yu RT, Brenner DA, Coulter S, Liddle C, Schoonjans K, Olefsky JM, Saltiel AR, Downes M, Evans RM. Intestinal FXR agonism promotes adipose tissue browning and reduces obesity and insulin resistance. Nat Med. 2015;21(2):159–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Kliewer SA, Mangelsdorf DJ. Bile acids as hormones: the FXR-FGF15/19 pathway. Dig Dis. 2015;33(3):327–31.

    Article  PubMed  PubMed Central  Google Scholar 

  87. Thomas C, Gioiello A, Noriega L, Strehle A, Oury J, Rizzo G, Macchiarulo A, Yamamoto H, Mataki C, Pruzanski M, Pellicciari R, Auwerx J, Schoonjans K. TGR5-mediated bile acid sensing controls glucose homeostasis. Cell Metab. 2009;10:167–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Beiroa D, Imbernon M, Gallego R, Senra A, Herranz D, Villarroya F, Serrano M, Fernø J, Salvador J, Escalada J, Dieguez C, Lopez M, Frühbeck G, Nogueiras R. GLP-1 agonism stimulates brown adipose tissue thermogenesis and browning through hypothalamic AMPK. Diabetes. 2014;63(10):3346–58.

    Article  CAS  PubMed  Google Scholar 

  89. Hu J, Kyrou I, Tan BK, Dimitriadis GK, Ramanjaneya M, Tripathi G, Patel V, James S, Kawan M, Chen J, Randeva HS. Short-chain fatty acid acetate stimulates Adipogenesis and mitochondrial biogenesis via GPR43 in Brown adipocytes. Endocrinology. 2016;157(5):1881–94.

    Article  CAS  PubMed  Google Scholar 

  90. Velickovic K, Cvoro A, Srdic B, et al. Expression and subcellular localization of estrogen receptors alpha and Beta in human fetal brown adipose tissue. J Clin Endocrinol Metab. 2014;99:151–9.

    Article  CAS  PubMed  Google Scholar 

  91. Xu Y, Nedungadi TP, Zhu L, et al. Distinct hypothalamic neurons mediate estrogenic effects on energy homeostasis and reproduction. Cell Metab. 2011;14:453–65.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Martínez de Morentin PB, Lage R, González-García I, Ruíz-Pino F, Martins L, Fernández-Mallo D, Gallego R, Fernø J, Señarís R, Saha AK, Tovar S, Diéguez C, Nogueiras R, Tena-Sempere M, López M. Pregnancy induces resistance to the anorectic effect of hypothalamic malonyl-CoA and the thermogenic effect of hypothalamic AMPK inhibition in female rats. Endocrinology. 2015;156(3):947–60.

    Article  PubMed  CAS  Google Scholar 

  93. Usui T, Kajita K, Kajita T, Mori I, Hanamoto T, Ikeda T, Okada H, Taguchi K, Kitada Y, Morita H, Sasaki T, Kitamura T, Sato T, Kojima I, Ishizuka T. Elevated mitochondrial biogenesis in skeletal muscle is associated with testosterone-induced body weight loss in male mice. FEBS Lett. 2014;588(10):1935–41.

    Article  CAS  PubMed  Google Scholar 

  94. Deng J, Schoeneman SE, Zhang H, Kwon S, Rigsby CK, Shore RM, Josefson JL. MRI characterization of brown adipose tissue in obese and normal-weight children. Pediatr Radiol. 2015;45(11):1682–9.

    Article  PubMed  Google Scholar 

  95. Bombardier E, Smith IC, Gamu D, Fajardo VA, Vigna C, Sayer RA, Gupta SC, Bal NC, Periasamy M, Tupling AR. Sarcolipin trumps β-adrenergic receptor signaling as the favored mechanism for muscle-based diet-induced thermogenesis. FASEB J. 2013;27(9):3871–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Vosselman MJ, Brans B, van der Lans AA, Wierts R, van Baak MA, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD. Brown adipose tissue activity after a high-calorie meal in humans. Am J Clin Nutr. 2013;98(1):57–64.

    Article  CAS  PubMed  Google Scholar 

  97. Tappy L. Thermic effect of food and sympathetic nervous system activity in humans. Reprod Nutr Dev. 1996;36(4):391–7.

    Article  CAS  PubMed  Google Scholar 

  98. Quatela A, Callister R, Patterson A, MacDonald-Wicks L. The energy content and composition of meals consumed after an overnight fast and their effects on diet induced thermogenesis: a systematic review, meta-analyses and meta-regressions. Forum Nutr. 2016;8(11):E670.

    Google Scholar 

  99. Carneiro IP, Elliott SA, Siervo M, Padwal R, Bertoli S, Battezzati A, Prado CM. Is obesity associated with altered energy expenditure? Adv Nutr. 2016;7(3):476–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Maffeis C, Schutz Y, Zoccante L, Micciolo R, Pinelli L. Meal-induced thermogenesis in lean and obese prepubertal children. Am J Clin Nutr. 1993;57(4):481–5.

    CAS  PubMed  Google Scholar 

  101. Tappy L, Egli L, Lecoultre V, Schneider P. Effects of fructose-containing caloric sweeteners on resting energy expenditure and energy efficiency: a review of human trials. Nutr Metab (Lond). 2013;10(1):54.

    Article  CAS  Google Scholar 

  102. Yoneshiro T, Aita S, Kawai Y, Iwanaga T, Saito M. Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr. 2012;95(4):845–50.

    Article  CAS  PubMed  Google Scholar 

  103. Yuan X, Wei G, You Y, Huang Y, Lee HJ, Dong M, Lin J, Hu T, Zhang H, Zhang C, Zhou H, Ye R, Qi X, Zhai B, Huang W, Liu S, Xie W, Liu Q, Liu X, Cui C, Li D, Zhan J, Cheng J, Yuan Z, Jin W. Rutin ameliorates obesity through brown fat activation. FASEB J. 2017;31(1):333–45.

    Article  CAS  PubMed  Google Scholar 

  104. Sugita J, Yoneshiro T, Hatano T, Aita S, Ikemoto T, Uchiwa H, Iwanaga T, Kameya T, Kawai Y, Saito M. Grains of paradise (Aframomum Melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men. Br J Nutr. 2013;110(4):733–8.

    Article  CAS  PubMed  Google Scholar 

  105. Ahmad NN, Pfalzer A, Kaplan LM. Roux-en-Y gastric bypass normalizes the blunted postprandial bile acid excursion associated with obesity. Int J Obes. 2013;37(12):1553–9.

    Article  CAS  Google Scholar 

  106. Changchien EM, Ahmed S, Betti F, Higa J, Kiely K, Hernandez-Boussard T, Morton J. B-type natriuretic peptide increases after gastric bypass surgery and correlates with weight loss. Surg Endosc. 2011;25(7):2338–43.

    Article  PubMed  Google Scholar 

  107. Neinast MD, Frank AP, Zechner JF, Li Q, Vishvanath L, Palmer BF, Aguirre V, Gupta RK, Clegg DJ. Activation of natriuretic peptides and the sympathetic nervous system following roux-en-Y gastric bypass is associated with gonadal adipose tissues browning. Mol Metab. 2015;4(5):427–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. Mulya A, Kirwan JP. Brown and Beige adipose tissue: therapy for obesity and its comorbidities? Endocrinol Metab Clin N Am. 2016;45(3):605–21.

    Article  Google Scholar 

  109. Dai YN, Zhu JZ, Fang ZY, Zhao DJ, Wan XY, Zhu HT, Yu CH, Li YM. A case-control study: association between serum neuregulin 4 level and non-alcoholic fatty liver disease. Metabolism. 2015;64(12):1667–73.

    Article  CAS  PubMed  Google Scholar 

  110. Wang GX, Zhao XY, Meng ZX, Kern M, Dietrich A, Chen Z, Cozacov Z, Zhou D, Okunade AL, Su X, Li S, Blüher M, Lin JD. The brown fat-enriched secreted factor Nrg4 preserves metabolic homeostasis through attenuation of hepatic lipogenesis. Nat Med. 2014;20(12):1436–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Villarroya F, Cereijo R, Villarroya J, Giralt M. Brown adipose tissue as a secretory organ. Nat Rev Endocrinol. 2017;13(1):26–35.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael Freemark MD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Freemark, M., Collins, S. (2018). Brown Adipose Tissue and Body Weight Regulation. In: Freemark, M. (eds) Pediatric Obesity. Contemporary Endocrinology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-68192-4_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-68192-4_7

  • Published:

  • Publisher Name: Humana Press, Cham

  • Print ISBN: 978-3-319-68191-7

  • Online ISBN: 978-3-319-68192-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics