Skip to main content Accessibility help

Adipose tissue development during early life: novel insights into energy balance from small and large mammals

  • Michael E. Symonds (a1), Mark Pope (a1) and Helen Budge (a1)


Since the rediscovery of brown adipose tissue (BAT) in adult human subjects in 2007, there has been a dramatic resurgence in research interest in its role in heat production and energy balance. This has coincided with a reassessment of the origins of BAT and the suggestion that brown preadipocytes could share a common lineage with skeletal myoblasts. In precocial newborns, such as sheep, the onset of non-shivering thermogenesis through activation of the BAT-specific uncoupling protein 1 (UCP1) is essential for effective adaptation to the cold exposure of the extra-uterine environment. This is mediated by a combination of endocrine adaptations which accompany normal parturition at birth and further endocrine stimulation from the mother's milk. Three distinct adipose depots have been identified in all species studied to date. These contain either primarily white, primarily brown or a mix of brown and white adipocytes. The latter tissue type is present, at least, in the fetus and, thereafter, appears to take on the characteristics of white adipose tissue during postnatal development. It is becoming apparent that a range of organ-specific mechanisms can promote UCP1 expression. They include the liver, heart and skeletal muscle, and involve unique endocrine systems that are stimulated by cold exposure and/or exercise. These multiple pathways that promote BAT function vary with age and between species that may determine the potential to be manipulated in early life. Such interventions could modify, or reverse, the normal ontogenic pathway by which BAT disappears after birth, thereby facilitating BAT thermogenesis through the life cycle.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Adipose tissue development during early life: novel insights into energy balance from small and large mammals
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Adipose tissue development during early life: novel insights into energy balance from small and large mammals
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Adipose tissue development during early life: novel insights into energy balance from small and large mammals
      Available formats


Corresponding author

* Corresponding author: Professor Michael E. Symonds, fax +44 115 823 0626, email


Hide All
1. Nedergaard, J, Bengtsson, T & Cannon, B (2007) Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 293, E444–E452.
2. Nedergaard, J, Bengtsson, T & Cannon, B (2010) Three years with adult human brown adipose tissue. Ann N Y Acad Sci 1212, E20E36.
3. Symonds, ME, Pope, M, Sharkey, D et al. . (2012) Adipose tissue and fetal programming. Diabetologia 55(6), 15971606.
4. Symonds, ME, Sebert, S & Budge, H (2011) The obesity epidemic: from the environment to epigenetics – not simply a response to dietary manipulation in a thermoneutral environment. Front Epigenom 2, 24, doi: 10.3389/fgene.2011. 00024
5. Cypess, AM, Lehman, S, Williams, G et al. . (2009) Identification and importance of brown adipose tissue in adult humans. N Engl J Med 360, 15091517.
6. van Marken Lichtenbelt, WD, Vanhommerig, JW, Smulders, NM et al. . (2009) Cold-activated brown adipose tissue in healthy men. N Engl J Med 360, 15001508.
7. Virtanen, KA, Lidell, ME, Orava, J et al. . (2009) Functional brown adipose tissue in healthy adults. N Engl J Med 360, 15181525.
8. Aherne, W & Hull, D (1966) Brown adipose tissue and heat production in the newborn infant. J Pathol Bacteriol 91, 223234.
9. Hu, HH, Tovar, JP, Pavlova, Z et al. (2011) Unequivocal identification of brown adipose tissue in a human infant. J Magn Reson Imag 35(4), 938942.
10. Clarke, L, Heasman, L, Firth, K et al. . (1997) Influence of route of delivery and ambient temperature on thermoregulation in newborn lambs. Am J Physiol Regul Integr Comp Physiol 272, R1931–R1939.
11. Power, G (1989) Biology of temperature: the mammalian fetus. J Dev Physiol 12, 295304.
12. Symonds, ME, Budge, H, Perkins, AC et al. . (2011) Adipose tissue development – impact of the early life environment. Prog Biophys Mol Biol 106, 300306.
13. Rothwell, NJ & Stock, MJ (1979) A role for brown adipose tissue in diet-induced thermogenesis. Nature 281, 3135.
14. Rothwell, NJ & Stock, MJ (1983) Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci (Lond) 64, 1923.
15. Cannon, B & Nedergaard, J (2012) Yes, even human brown fat is on fire! J Clin Invest 122(2), 486489.
16. Cannon, B & Nedergaard, J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84, 277359.
17. Seale, P, Bjork, B, Yang, W et al. . (2008) PRDM16 controls a brown fat/skeletal muscle switch. Nature 454, 961967.
18. Petrovic, N, Walden, TB, Shabalina, IG et al. . (2010) Chronic peroxisome proliferator-activated receptor gamma 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, 71537164.
19. Fromme, T & Klingenspor, M (2011) Uncoupling protein 1 expression and high-fat diets. Am J Physiol Regul Integr Comp Physiol 300, R18.
20. Symonds, ME, Bird, JA, Clarke, L et al. . (1995) Nutrition, temperature and homeostasis during perinatal development. Exp Phys 80, 907940.
21. Cannon, B, Connoley, E, Obregon, M-J et al. . (1988) Perinatal activation of brown adipose tissue. In The Endocrine Control of the Fetus, pp. 306320 [Kunzel, W & Jesen, A, editors]. Berlin: Springer Verlag.
22. Charalambous, M, Ferron, SR, da Rocha, ST et al. . (2012) Imprinted gene dosage is critical for the transition to independent life. Cell Metab 15, 209221.
23. Hall, JA, Ribich, S, Christoffolete, MA et al. . (2010) Absence of thyroid hormone activation during development underlies a permanent defect in adaptive thermogenesis. Endocrinology 151, 45734582.
24. Schermer, SJ, Bird, JA, Lomax, MA et al. . (1996) Effect of fetal thyroidectomy on brown adipose tissue and thermoregulation in newborn lambs. Reprod Fertil Dev 8, 9951002.
25. Lee, JY, Takahashi, N, Yasubuchi, M et al. . (2012) Triiodothyronine induces UCP-1 expression and mitochondrial biogenesis in human adipocytes. Am J Physiol Cell Physiol 302, C463–C472.
26. Symonds, ME, Mostyn, A, Pearce, S et al. . (2003) Endocrine and nutritional regulation of fetal adipose tissue development. J Endocrinol 179, 293299.
27. Clarke, L, Buss, DS, Juniper, DS et al. . (1997) Adipose tissue development during early postnatal life in ewe-reared lambs. Exp Phys 82, 10151017.
28. Mostyn, A, Wilson, V, Dandrea, J et al. . (2003) Ontogeny and nutritional manipulation of mitochondrial protein abundance in adipose tissue and the lungs of postnatal sheep. Br J Nutr 90, 323328.
29. Bispham, J, Budge, H, Mostyn, A et al. . (2002) Ambient temperature, maternal dexamethasone, and postnatal ontogeny of leptin in the neonatal lamb. Pediatr Res 52, 8590.
30. Walden, TB, Hansen, IR, Timmons, JA et al. . (2012) Recruited vs. nonrecruited molecular signatures of brown, “brite”, and white adipose tissues. Am J Physiol Endocrinol Metab 302, E19–E31.
31. Tseng, YH, Kokkotou, E, Schulz, TJ et al. . (2008) New role of bone morphogenetic protein 7 in brown adipogenesis and energy expenditure. Nature 454, 10001004.
32. Dessolin, S, Schalling, M, Champigny, O et al. . (1997) Leptin gene is expressed in rat brown adipose tissue at birth. FASEB J 11, 382387.
33. Nicholas, KR & Hartmann, PE (1991) Milk secretion in the rat: progressive changes in milk composition during lactation and weaning and the effect of diet. Comp Biochem Physiol A Comp Physiol 98, 535542.
34. Fulkerson, WJ & McDowell, GH (1974) Effect of oestrogen administered in early or late lactation on the yield and composition of milk in sheep. J Endocrinol 63, 175180.
35. Kulski, JK & Hartmann, PE (1981) Changes in human milk composition during the initiation of lactation. Aust J Exp Biol Med Sci 59, 101114.
36. Perez, MD, Sanchez, L, Aranda, P et al. . (1990) Synthesis and evolution of concentration of beta-lactoglobulin and alpha-lactalbumin from cow and sheep colostrum and milk throughout early lactation. Cell Mol Biol 36, 205212.
37. Kulski, JK & Hartmann, PE (1981) Changes in the concentration of cortisol in milk during different stages of human lactation. Aust J Exp Biol Med Sci 59, 769778.
38. Mostyn, A, Pearce, S, Budge, H et al. . (2003) Influence of cortisol on adipose tissue development in the fetal sheep during late gestation. J Endocrinol 176, 2330.
39. Banchero, GE, Quintans, G, Martin, GB et al. . (2004) Nutrition and colostrum production in sheep. 1. Metabolic and hormonal responses to a high-energy supplement in the final stages of pregnancy. Reprod Fertil Dev 16, 633643.
40. Macy, IG (1949) Composition of human colostrum and milk. Am J Dis Child 78, 589603.
41. Michaelsen, KF, Skafte, L, Badsberg, JH et al. . (1990) Variation in macronutrients in human bank milk: influencing factors and implications for human milk banking. J Pediatr Gastroenterol Nutr 11, 229239.
42. Cregan, MD, Mitoulas, LR & Hartmann, PE (2002) Milk prolactin, feed volume and duration between feeds in women breastfeeding their full-term infants over a 24 h period. Exp Physiol 87, 207214.
43. Symonds, ME, Sebert, SP & Budge, H (2010) Nutritional regulation of fetal growth and implications for productive life in ruminants. Animal 4, 10571083.
44. Pearce, S, Budge, H, Mostyn, A et al. . (2005) Prolactin, the prolactin receptor and uncoupling protein abundance and function in adipose tissue during development in young sheep. J Endocrinol 184, 351359.
45. Li, R, Fein, SB & Grummer-Strawn, LM (2010) Do infants fed from bottles lack self-regulation of milk intake compared with directly breastfed infants? Pediatrics 125, e1386–e1393.
46. Townsend, E & Pitchford, NJ (2012) Baby knows best? The impact of weaning style on food preferences and body mass index in early childhood in a case-controlled sample. BMJ Open 2, e000298.
47. Crume, TL, Ogden, LG, Mayer-Davis, EJ et al. (2012) The impact of neonatal breast-feeding on growth trajectories of youth exposed and unexposed to diabetes in utero: the EPOCH Study. Int J Obes (Lond) 36(4), 529534.
48. Fukuchi, K, Ono, Y, Nakahata, Y et al. . (2003) Visualization of interscapular brown adipose tissue using (99 m)Tc-tetrofosmin in pediatric patients. J Nucl Med 44, 15821585.
49. Hadi, M, Chen, CC, Whatley, M et al. . (2007) Brown fat imaging with (18)F-6-fluorodopamine PET/CT, (18)F-FDG PET/CT, and (123)I-MIBG SPECT: a study of patients being evaluated for pheochromocytoma. J Nucl Med 48, 10771083.
50. Thackeray, JT, Beanlands, RS & Dasilva, JN (2007) Presence of specific 11C-meta-Hydroxyephedrine retention in heart, lung, pancreas, and brown adipose tissue. J Nucl Med 48, 17331740.
51. Blessing, W, Mohammed, M & Ootsuka, Y (2012) Heating and eating: brown adipose tissue thermogenesis precedes food ingestion as part of the ultradian basic rest-activity cycle in rats. Physiol Behav 105, 966974.
52. Ouellet, V, Labbe, SM, Blondin, DP et al. (2012) Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 122(2), 545552.
53. Symonds, ME, Henderson, K, Elvidge, L et al. . (2012) Thermal imaging to assess age-related changes of skin temperature within the supraclavicular region co-locating with brown adipose tissue in healthy children. J Pediatr (In the Press).
54. Scazzina, F, Del Rio, D, Benini, L et al. . (2010) The effect of breakfasts varying in glycemic index and glycemic load on dietary induced thermogenesis and respiratory quotient. Nutr Metab Cardiovasc Dis 21, 121125.
55. Westerterp, KR, Wilson, SA & Rolland, V (1999) Diet induced thermogenesis measured over 24 h in a respiration chamber: effect of diet composition. Int J Obes Relat Metab Disord 23, 287292.
56. Symonds, ME, Phillips, ID, Anthony, RV et al. . (1998) Prolactin receptor gene expression and foetal adipose tissue. J Neuroendocrinol 10, 885890.
57. Bispham, J, Heasman, L, Clarke, L et al. . (1999) Effect of maternal dexamethasone treatment and ambient temperature on prolactin receptor abundance in Brown adipose and hepatic tissue in the foetus and new-born lamb. J Neuroendocrinol 11, 849856.
58. Budge, H, Bispham, J, Dandrea, J et al. . (2000) Effect of maternal nutrition on brown adipose tissue and prolactin receptor status in the fetal lamb. Pediatr Res 47, 781786.
59. Auchtung, TL, Rius, AG, Kendall, PE et al. . (2005) Effects of photoperiod during the dry period on prolactin, prolactin receptor, and milk production of dairy cows. J Dairy Sci 88, 121127.
60. Au-Yong, IT, Thorn, N, Ganatra, R et al. . (2009) Brown adipose tissue and seasonal variation in humans. Diabetes 58, 25832587.
61. Cohick, CB, Dai, G, Xu, L et al. . (1996) Placental lactogen-I variant utilizes the prolactin receptor signaling pathway. Mol Cell Endocrinol 116, 4958.
62. Fowlkes, J & Freemark, M (1992) Binding of placental lactogen and growth hormone to fetal sheep fibroblasts. Pediatr Res 32, 200203.
63. Fielder, PJ & Talamantes, F (1987) The lipolytic effects of mouse placental lactogen II, mouse prolactin, and mouse growth hormone on adipose tissue from virgin and pregnant mice. Endocrinology 121, 493497.
64. Campbell, RM, Kostyo, JL & Scanes, CG (1990) Lipolytic and antilipolytic effects of human growth hormone, its 20-kilodalton variant, a reduced and carboxymethylated derivative, and human placental lactogen on chicken adipose tissue in vitro. Proc Soc Exp Biol Med 193, 269273.
65. Viengchareun, S, Servel, N, Feve, B et al. . (2008) Prolactin receptor signaling is essential for perinatal brown adipocyte function: a role for insulin-like growth factor-2. PLoS ONE 3, e1535.
66. Soares, MJ (2004) The prolactin and growth hormone families: pregnancy-specific hormones/cytokines at the maternal-fetal interface. Reprod Biol Endocrinol 2, 51.
67. Helliwell, RJ, Wallace, JM, Aitken, RP et al. . (1997) The effect of prenatal photoperiodic history on the postnatal endocrine status of female lambs. Anim Reprod Sci 47, 303314.
68. Meyre, D, Delplanque, J, Chevre, JC et al. . (2009) Genome-wide association study for early-onset and morbid adult obesity identifies three new risk loci in European populations. Nat Genet 41, 157159.
69. Nilsson, L, Olsson, AH, Isomaa, B et al. . (2011) A common variant near the PRL gene is associated with increased adiposity in males. Mol Genet Metab 102, 7881.
70. Kok, P, Roelfsema, F, Frolich, M et al. . (2006) Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women. Am J Physiol Endocrinol Metab 291, E1038E1043.
71. Hondares, E, Rosell, M, Gonzalez, FJ et al. . (2010) Hepatic FGF21 expression is induced at birth via PPARalpha in response to milk intake and contributes to thermogenic activation of neonatal brown fat. Cell Metab 11, 206212.
72. Fisher, FM, Kleiner, S, Douris, N et al. . (2012) FGF21 regulates PGC-1alpha and browning of white adipose tissues in adaptive thermogenesis. Genes Dev 26, 271281.
73. Wei, W, Dutchak, PA, Wang, X et al. (2012) Fibroblast growth factor 21 promotes bone loss by potentiating the effects of peroxisome proliferator-activated receptor γ. Proc Natl Acad Sci USA 109(8), 31433148.
74. Whittle, AJ & Vidal-Puig, A (2012) NPs – heart hormones that regulate brown fat? J Clin Invest 122, 804807.
75. Bostrom, P, Wu, J, Jedrychowski, MP et al. . (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481, 463468.
76. Bordicchia, M, Liu, D, Amri, EZ et al. . (2012) Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. J Clin Invest 122, 10221036.
77. Sacks, HS, Fain, JN, Holman, B et al. . (2009) Uncoupling protein-1 and related messenger ribonucleic acids in human epicardial and other adipose tissues: epicardial fat functioning as brown fat. J Clin Endocrinol Metab 94, 36113615.
78. Rudolph, AM (1985) Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res 57, 811821.
79. Vogt, N & Seiler, S (2008) The RHO1-specific GTPase-activating protein LRG1 regulates polar tip growth in parallel to Ndr kinase signaling in Neurospora. Mol Biol Cell 19, 45544569.
80. Li, Y, Zhang, Y, Qiu, F et al. . (2011) Proteomic identification of exosomal LRG1: a potential urinary biomarker for detecting NSCLC. Electrophoresis 32, 19761983.
81. Ladd, J, Busald Buson, T, Johnson, M et al. (2012) Increased plasma levels of the APC-interacting protein MAPRE1, LRG1 and IGFBP2 preceding a diagnosis of colorectal cancer in women. Cancer Prev Res 5(4), 655664.
82. Bing, C, Brown, M, King, P et al. . (2000) Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle UCP2 and UCP3 in MAC16-induced cancer cachexia. Cancer Res 60, 24052410.
83. Gunn, T & Gluckman, PD (1995) Perinatal thermogenesis. Early Hum Dev 42, 169183.
84. Alexander, G & Williams, D (1968) Shivering and nonshivering thermogenesis during summit metabolism in young lambs. J Physiol (Lond) 198, 251276.
85. Symonds, ME, Andrews, DC & Johnson, PJ (1989) The control of thermoregulation in the developing lamb during slow wave sleep. J Dev Physiol 11, 289298.


Adipose tissue development during early life: novel insights into energy balance from small and large mammals

  • Michael E. Symonds (a1), Mark Pope (a1) and Helen Budge (a1)


Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed