In Vivo Detection of Human Brown Adipose Tissue During Cold and Exercise by PET/CT

  • Emmani B. M. Nascimento
  • Wouter D. van Marken LichtenbeltEmail author
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 251)


The role of brown adipose tissue (BAT) in non-shivering thermogenesis is well established in animals. BAT is activated following cold exposure, resulting in non-shivering thermogenesis, to ensure a constant body temperature. In mitochondria of brown adipocytes, glucose and fatty acids are used as substrate for uncoupling resulting in heat production. Activated BAT functions as a sink for glucose and fatty acids and this hallmark has designated BAT a target in the fight against metabolic diseases like type 2 diabetes mellitus and obesity. In order to make valid claims regarding BAT activity in humans, BAT activity needs to be quantified. The combination of positron emission tomography (PET) and computer tomography (CT) analysis is currently the most frequently used imaging technique to determine BAT activity in humans. Here, we will discuss the history of PET/CT and radioisotopes used to determine BAT activity in humans. Moreover, we will assess how PET/CT is used to determine BAT activity following cold and exercise.


[18F]FDG [18F]FTHA Brown adipose tissue Cold Exercise PET/CT Radioisotope 


  1. Albrecht E, Norheim F, Thiede B, Holen T, Ohashi T, Schering L, Lee S, Brenmoehl J, Thomas S, Drevon CA, Erickson HP, Maak S (2015) Irisin – a myth rather than an exercise-inducible myokine. Sci Rep 5:8889. CrossRefPubMedPubMedCentralGoogle Scholar
  2. Aldiss P, Betts J, Sale C, Pope M, Symonds ME (2017) Exercise-induced ‘browning’ of adipose tissues. Metabolism 81:63–70. CrossRefPubMedGoogle Scholar
  3. Bauwens M, Wierts R, van Royen B, Bucerius J, Backes W, Mottaghy F, Brans B (2014) Molecular imaging of brown adipose tissue in health and disease. Eur J Nucl Med Mol Imaging 41:776–791. CrossRefPubMedGoogle Scholar
  4. Blondin DP, Labbe SM, Tingelstad HC, Noll C, Kunach M, Phoenix S, Guerin B, Turcotte EE, Carpentier AC, Richard D, Haman F (2014) Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab 99:E438–E446. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Blondin DP, Labbé SM, Noll C, Kunach M, Phoenix S, Guérin B, Turcotte ÉE, Haman F, Richard D, Carpentier AC (2015) Selective impairment of glucose but not fatty acid or oxidative metabolism in brown adipose tissue of subjects with type 2 diabetes. Diabetes 64(7):2388–2397. CrossRefPubMedGoogle Scholar
  6. Blondin DP, Tingelstad HC, Noll C, Frisch F, Phoenix S, Guerin B, Turcotte EE, Richard D, Haman F, Carpentier AC (2017) Dietary fatty acid metabolism of brown adipose tissue in cold-acclimated men. Nat Commun 8:14146. CrossRefPubMedPubMedCentralGoogle Scholar
  7. Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, Rasbach KA, Bostrom EA, Choi JH, Long JZ, Kajimura S, Zingaretti MC, Vind BF, Tu H, Cinti S, Hojlund K, Gygi SP, Spiegelman BM (2012) A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature 481:463–468. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Broeders EP, Nascimento EB, Havekes B, Brans B, Roumans KH, Tailleux A, Schaart G, Kouach M, Charton J, Deprez B, Bouvy ND, Mottaghy F, Staels B, van Marken Lichtenbelt WD, Schrauwen P (2015) The bile acid chenodeoxycholic acid increases human brown adipose tissue activity. Cell Metab 22:418–426. CrossRefPubMedGoogle Scholar
  9. Burcelin R, Kande J, Ricquier D, Girard J (1993) Changes in uncoupling protein and GLUT4 glucose transporter expressions in interscapular brown adipose tissue of diabetic rats: relative roles of hyperglycaemia and hypoinsulinaemia. Biochem J 291(Pt 1):109–113CrossRefGoogle Scholar
  10. Cannon B, Nedergaard J (2004) Brown adipose tissue: function and physiological significance. Physiol Rev 84:277–359. CrossRefPubMedGoogle Scholar
  11. Charron M, Beyer T, Bohnen NN, Kinahan PE, Dachille M, Jerin J, Nutt R, Meltzer CC, Villemagne V, Townsend DW (2000) Image analysis in patients with cancer studied with a combined PET and CT scanner. Clin Nucl Med 25:905–910CrossRefGoogle Scholar
  12. Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA, Enerback S, Kinahan PE, Lichtenbelt W, Lin FI, Sunderland JJ, Virtanen KA, Wahl RL (2016) Brown Adipose Reporting Criteria in Imaging STudies (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab 24:210–222. CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chondronikola M, Volpi E, Borsheim E, Chao T, Porter C, Annamalai P, Yfanti C, Labbe SM, Hurren NM, Malagaris I, Cesani F, Sidossis LS (2016) Brown adipose tissue is linked to a distinct thermoregulatory response to mild cold in people. Front Physiol 7:129. CrossRefPubMedPubMedCentralGoogle Scholar
  14. Chondronikola M, Beeman SC, Wahl RL (2018) Non-invasive methods for the assessment of brown adipose tissue in humans. J Physiol 596:363–378. CrossRefPubMedPubMedCentralGoogle Scholar
  15. Cohade C, Mourtzikos KA, Wahl RL (2003a) “USA-Fat”: prevalence is related to ambient outdoor temperature-evaluation with 18F-FDG PET/CT. J Nucl Med 44:1267–1270PubMedGoogle Scholar
  16. Cohade C, Osman M, Pannu HK, Wahl RL (2003b) Uptake in supraclavicular area fat (“USA-Fat”): description on 18F-FDG PET/CT. J Nucl Med 44:170–176PubMedPubMedCentralGoogle Scholar
  17. Coker RH, Weaver AN, Coker MS, Murphy CJ, Gunga HC, Steinach M (2017) Metabolic responses to the Yukon Arctic ultra: longest and coldest in the world. Med Sci Sports Exerc 49:357–362. CrossRefPubMedPubMedCentralGoogle Scholar
  18. Cuevas-Ramos D, Almeda-Valdes P, Meza-Arana CE, Brito-Cordova G, Gomez-Perez FJ, Mehta R, Oseguera-Moguel J, Aguilar-Salinas CA (2012) Exercise increases serum fibroblast growth factor 21 (FGF21) levels. PLoS One 7:e38022. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 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 360:1509–1517. CrossRefPubMedPubMedCentralGoogle Scholar
  20. Cypess AM, Chen YC, Sze C, Wang K, English J, Chan O, Holman AR, Tal I, Palmer MR, Kolodny GM, Kahn CR (2012) Cold but not sympathomimetics activates human brown adipose tissue in vivo. Proc Natl Acad Sci U S A 109:10001–10005. CrossRefPubMedPubMedCentralGoogle Scholar
  21. Cypess AM, Weiner LS, Roberts-Toler C, Franquet Elia E, Kessler SH, Kahn PA, English J, Chatman K, Trauger SA, Doria A, Kolodny GM (2015) Activation of human brown adipose tissue by a beta3-adrenergic receptor agonist. Cell Metab 21:33–38. CrossRefPubMedPubMedCentralGoogle Scholar
  22. DeGrado TR, Coenen HH, Stocklin G (1991) 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid (FTHA): evaluation in mouse of a new probe of myocardial utilization of long chain fatty acids. J Nucl Med 32:1888–1896PubMedPubMedCentralGoogle Scholar
  23. Deng J, Neff LM, Rubert NC, Zhang B, Shore RM, Samet JD, Nelson PC, Landsberg L (2017) MRI characterization of brown adipose tissue under thermal challenges in normal weight, overweight, and obese young men. J Magn Reson Imaging 47(4):936–947. CrossRefPubMedPubMedCentralGoogle Scholar
  24. Din M, Raiko J, Saari T, Kudomi N, Tolvanen T, Oikonen V, Teuho J, Sipila HT, Savisto N, Parkkola R, Nuutila P, Virtanen KA (2016) Human brown adipose tissue [(15)O]O2 PET imaging in the presence and absence of cold stimulus. Eur J Nucl Med Mol Imaging 43:1878–1886. CrossRefGoogle Scholar
  25. Dinas PC, Nikaki A, Jamurtas AZ, Prassopoulos V, Efthymiadou R, Koutedakis Y, Georgoulias P, Flouris AD (2015) Association between habitual physical activity and brown adipose tissue activity in individuals undergoing PET-CT scan. Clin Endocrinol 82:147–154. CrossRefGoogle Scholar
  26. Ebert A, Herzog H, Stocklin GL, Henrich MM, DeGrado TR, Coenen HH, Feinendegen LE (1994) Kinetics of 14(R,S)-fluorine-18-fluoro-6-thia-heptadecanoic acid in normal human hearts at rest, during exercise and after dipyridamole injection. J Nucl Med 35:51–56PubMedGoogle Scholar
  27. Flouris AD, Dinas PC, Valente A, Andrade CMB, Kawashita NH, Sakellariou P (2017) Exercise-induced effects on UCP1 expression in classical brown adipose tissue: a systematic review. Horm Mol Biol Clin Invest 31.
  28. Hansen JS, Pedersen BK, Xu G, Lehmann R, Weigert C, Plomgaard P (2016) Exercise-induced secretion of FGF21 and follistatin are blocked by pancreatic clamp and impaired in type 2 diabetes. J Clin Endocrinol Metab 101:2816–2825. CrossRefPubMedGoogle Scholar
  29. Hanssen MJ, Wierts R, Hoeks J, Gemmink A, Brans B, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD (2015) Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance. Diabetologia 58:586–595. CrossRefPubMedGoogle Scholar
  30. Hanssen MJ, van der Lans AA, Brans B, Hoeks J, Jardon KM, Schaart G, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD (2016) Short-term cold acclimation recruits brown adipose tissue in obese humans. Diabetes 65:1179–1189. CrossRefPubMedGoogle Scholar
  31. 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 29:1393–1398. CrossRefPubMedGoogle Scholar
  32. Hondares E, Iglesias R, Giralt A, Gonzalez FJ, Giralt M, Mampel T, Villarroya F (2011) Thermogenic activation induces FGF21 expression and release in brown adipose tissue. J Biol Chem 286:12983–12990. CrossRefPubMedPubMedCentralGoogle Scholar
  33. Iwen KA, Backhaus J, Cassens M, Waltl M, Hedesan OC, Merkel M, Heeren J, Sina C, Rademacher L, Windjager A, Haug AR, Kiefer FW, Lehnert H, Schmid SM (2017) Cold-induced brown adipose tissue activity alters plasma fatty acids and improves glucose metabolism in men. J Clin Endocrinol Metab 102:4226–4234. CrossRefPubMedGoogle Scholar
  34. Izumiya Y, Bina HA, Ouchi N, Akasaki Y, Kharitonenkov A, Walsh K (2008) FGF21 is an Akt-regulated myokine. FEBS Lett 582:3805–3810. CrossRefPubMedPubMedCentralGoogle Scholar
  35. Kim KH, Kim SH, Min YK, Yang HM, Lee JB, Lee MS (2013) Acute exercise induces FGF21 expression in mice and in healthy humans. PLoS One 8:e63517. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 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 (2014) Irisin and FGF21 are cold-induced endocrine activators of brown fat function in humans. Cell Metab 19:302–309. CrossRefPubMedGoogle Scholar
  37. Madar I, Naor E, Holt D, Ravert H, Dannals R, Wahl R (2015) Brown adipose tissue response dynamics: in vivo insights with the voltage sensor 18F-fluorobenzyl triphenyl phosphonium. PLoS One 10:e0129627. CrossRefPubMedPubMedCentralGoogle Scholar
  38. Marette A, Deshaies Y, Collet AJ, Tulp O, Bukowiecki LJ (1991) Major thermogenic defect associated with insulin resistance in brown adipose tissue of obese diabetic SHR/N-cp rats. Am J Phys 261:E204–E213. CrossRefGoogle Scholar
  39. Mercer SW, Trayhurn P (1984) The development of insulin resistance in brown adipose tissue may impair the acute cold-induced activation of thermogenesis in genetically obese (Ob/Ob) mice. Biosci Rep 4:933–940CrossRefGoogle Scholar
  40. Muzik O, Mangner TJ, Granneman JG (2012) Assessment of oxidative metabolism in brown fat using PET imaging. Front Endocrinol 3:15. CrossRefGoogle Scholar
  41. Nirengi S, Homma T, Inoue N, Sato H, Yoneshiro T, Matsushita M, Kameya T, Sugie H, Tsuzaki K, Saito M, Sakane N, Kurosawa Y, Hamaoka T (2016) Assessment of human brown adipose tissue density during daily ingestion of thermogenic capsinoids using near-infrared time-resolved spectroscopy. J Biomed Opt 21:091305. CrossRefPubMedGoogle Scholar
  42. Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, Scheinin M, Taittonen M, Niemi T, Enerback S, Virtanen KA (2011) Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab 14:272–279. CrossRefGoogle Scholar
  43. Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, Richard D (2011) Outdoor temperature, age, sex, body mass index, and diabetic status determine the prevalence, mass, and glucose-uptake activity of 18F-FDG-detected BAT in humans. J Clin Endocrinol Metab 96:192–199. CrossRefPubMedPubMedCentralGoogle Scholar
  44. Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, Haman F, Turcotte EE, Richard D, Carpentier AC (2012) Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest 122:545–552. CrossRefPubMedPubMedCentralGoogle Scholar
  45. Patlak CS, Blasberg RG (1985) Graphical evaluation of blood-to-brain transfer constants from multiple-time uptake data. Generalizations. J Cereb Blood Flow Metab 5:584–590. CrossRefPubMedGoogle Scholar
  46. Paulus A, Maenen M, Drude N, Nascimento EBM, van Marken Lichtenbelt WD, Mottaghy FM, Bauwens M (2017) Synthesis, radiosynthesis and in vitro evaluation of 18F-Bodipy-C16/triglyceride as a dual modal imaging agent for brown adipose tissue. PLoS One 12:e0182297. CrossRefPubMedPubMedCentralGoogle Scholar
  47. Ramage LE, Akyol M, Fletcher AM, Forsythe J, Nixon M, Carter RN, van Beek EJ, Morton NM, Walker BR, Stimson RH (2016) Glucocorticoids acutely increase brown adipose tissue activity in humans, revealing species-specific differences in UCP-1 regulation. Cell Metab 24:130–141. CrossRefPubMedPubMedCentralGoogle Scholar
  48. Raschke S, Elsen M, Gassenhuber H, Sommerfeld M, Schwahn U, Brockmann B, Jung R, Wisloff U, Tjonna AE, Raastad T, Hallen J, Norheim F, Drevon CA, Romacho T, Eckardt K, Eckel J (2013) Evidence against a beneficial effect of irisin in humans. PLoS One 8:e73680. CrossRefPubMedPubMedCentralGoogle Scholar
  49. Rothwell NJ, Stock MJ (1983) Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci (Lond) 64:19–23CrossRefGoogle Scholar
  50. 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. CrossRefPubMedPubMedCentralGoogle Scholar
  51. Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Gil A, Ruiz JR (2015a) Role of exercise in the activation of brown adipose tissue. Ann Nutr Metab 67:21–32. CrossRefPubMedGoogle Scholar
  52. Sanchez-Delgado G, Martinez-Tellez B, Olza J, Aguilera CM, Labayen I, Ortega FB, Chillon P, Fernandez-Reguera C, Alcantara JMA, Martinez-Avila WD, Munoz-Hernandez V, Acosta FM, Prados-Ruiz J, Amaro-Gahete FJ, Hidalgo-Garcia L, Rodriguez L, Ruiz YA, Ramirez-Navarro A, Muros-de Fuentes MA, Garcia-Rivero Y, Sanchez-Sanchez R, de Dios Beas Jimenez J, de Teresa C, Navarrete S, Lozano R, Brea-Gomez E, Rubio-Lopez J, Ruiz MR, Cano-Nieto A, Llamas-Elvira JM, Jimenez Rios JA, Gil A, Ruiz JR (2015b) Activating brown adipose tissue through exercise (ACTIBATE) in young adults: rationale, design and methodology. Contemp Clin Trials 45:416–425. CrossRefPubMedGoogle Scholar
  53. Seebacher F, Glanville EJ (2010) Low levels of physical activity increase metabolic responsiveness to cold in a rat (Rattus fuscipes). PLoS One 5:e13022. CrossRefPubMedPubMedCentralGoogle Scholar
  54. Singhal V, Maffazioli GD, Ackerman KE, Lee H, Elia EF, Woolley R, Kolodny G, Cypess AM, Misra M (2016) Effect of chronic athletic activity on brown fat in young women. PLoS One 11:e0156353. CrossRefPubMedPubMedCentralGoogle Scholar
  55. Slocum N, Durrant JR, Bailey D, Yoon L, Jordan H, Barton J, Brown RH, Clifton L, Milliken T, Harrington W, Kimbrough C, Faber CA, Cariello N, Elangbam CS (2013) Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment. Exp Toxicol Pathol 65:549–557. CrossRefPubMedGoogle Scholar
  56. Slusher AL, Whitehurst M, Zoeller RF, Mock JT, Maharaj M, Huang CJ (2015) Attenuated fibroblast growth factor 21 response to acute aerobic exercise in obese individuals. Nutr Metab Cardiovasc Dis 25:839–845. CrossRefPubMedGoogle Scholar
  57. Sokoloff L, Reivich M, Kennedy C, Des Rosiers MH, Patlak CS, Pettigrew KD, Sakurada O, Shinohara M (1977) The [14C]deoxyglucose method for the measurement of local cerebral glucose utilization: theory, procedure, and normal values in the conscious and anesthetized albino rat. J Neurochem 28:897–916CrossRefGoogle Scholar
  58. Steinberg JD, Vogel W, Vegt E (2017) Factors influencing brown fat activation in FDG PET/CT: a retrospective analysis of 15,000+ cases. Br J Radiol 90:20170093. CrossRefPubMedPubMedCentralGoogle Scholar
  59. Sun L, Camps SG, Goh HJ, Govindharajulu P, Schaefferkoetter JD, Townsend DW, Verma SK, Velan SS, Sun L, Sze SK, Lim SC, Boehm BO, Henry CJ, Leow MK (2018) Capsinoids activate brown adipose tissue (BAT) with increased energy expenditure associated with subthreshold 18-fluorine fluorodeoxyglucose uptake in BAT-positive humans confirmed by positron emission tomography scan. Am J Clin Nutr 107:62–70. CrossRefPubMedGoogle Scholar
  60. Talukdar S, Zhou Y, Li D, Rossulek M, Dong J, Somayaji V, Weng Y, Clark R, Lanba A, Owen BM, Brenner MB, Trimmer JK, Gropp KE, Chabot JR, Erion DM, Rolph TP, Goodwin B, Calle RA (2016) A long-acting FGF21 molecule, PF-05231023, decreases body weight and improves lipid profile in non-human primates and type 2 diabetic subjects. Cell Metab 23:427–440. CrossRefPubMedGoogle Scholar
  61. Taniguchi H, Tanisawa K, Sun X, Kubo T, Higuchi M (2016) Endurance exercise reduces hepatic fat content and serum fibroblast growth factor 21 levels in elderly men. J Clin Endocrinol Metab 101:191–198. CrossRefPubMedGoogle Scholar
  62. Tanimura Y, Aoi W, Takanami Y, Kawai Y, Mizushima K, Naito Y, Yoshikawa T (2016) Acute exercise increases fibroblast growth factor 21 in metabolic organs and circulation. Physiol Rep 4:e12828. CrossRefPubMedPubMedCentralGoogle Scholar
  63. Turner CA, Watson SJ, Akil H (2012) The fibroblast growth factor family: neuromodulation of affective behavior. Neuron 76:160–174. CrossRefPubMedPubMedCentralGoogle Scholar
  64. van der Lans AA, Hoeks J, Brans B, Vijgen GH, Visser MG, Vosselman MJ, Hansen J, Jorgensen JA, Wu J, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD (2013) Cold acclimation recruits human brown fat and increases nonshivering thermogenesis. J Clin Invest 123:3395–3403. CrossRefPubMedPubMedCentralGoogle Scholar
  65. van Marken Lichtenbelt WD, Schrauwen P (2011) Implications of nonshivering thermogenesis for energy balance regulation in humans. Am J Physiol Regul Integr Comp Physiol 301:R285–R296. CrossRefPubMedGoogle Scholar
  66. 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 360:1500–1508. CrossRefPubMedPubMedCentralGoogle Scholar
  67. 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 360:1518–1525. CrossRefPubMedPubMedCentralGoogle Scholar
  68. Vosselman MJ, van der Lans AA, Brans B, Wierts R, van Baak MA, Schrauwen P, van Marken Lichtenbelt WD (2012) Systemic beta-adrenergic stimulation of thermogenesis is not accompanied by brown adipose tissue activity in humans. Diabetes 61:3106–3113. CrossRefPubMedPubMedCentralGoogle Scholar
  69. Vosselman MJ, Hoeks J, Brans B, Pallubinsky H, Nascimento EB, van der Lans AA, Broeders EP, Mottaghy FM, Schrauwen P, van Marken Lichtenbelt WD (2015) Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int J Obes 39:1696–1702. CrossRefGoogle Scholar
  70. Wang N, Liu Y, Ma Y, Wen D (2017) High-intensity interval versus moderate-intensity continuous training: superior metabolic benefits in diet-induced obesity mice. Life Sci 191:122–131. CrossRefPubMedGoogle Scholar
  71. Yang SJ, Hong HC, Choi HY, Yoo HJ, Cho GJ, Hwang TG, Baik SH, Choi DS, Kim SM, Choi KM (2011) Effects of a three-month combined exercise programme on fibroblast growth factor 21 and fetuin-A levels and arterial stiffness in obese women. Clin Endocrinol 75:464–469. CrossRefGoogle Scholar
  72. Yoneshiro T, Aita S, Kawai Y, Iwanaga T, Saito M (2012) Nonpungent capsaicin analogs (capsinoids) increase energy expenditure through the activation of brown adipose tissue in humans. Am J Clin Nutr 95:845–850. CrossRefPubMedGoogle Scholar
  73. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y, Iwanaga T, Saito M (2013) Recruited brown adipose tissue as an antiobesity agent in humans. J Clin Invest 123:3404–3408. CrossRefPubMedPubMedCentralGoogle Scholar
  74. Yoshioka K, Yoshida T, Wakabayashi Y, Nishioka H, Kondo M (1989) The role of insulin in norepinephrine turnover and thermogenesis in brown adipose tissue after acute cold-exposure. Endocrinol Jpn 36:491–499CrossRefGoogle Scholar

Copyright information

©  Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Emmani B. M. Nascimento
    • 1
  • Wouter D. van Marken Lichtenbelt
    • 1
    Email author
  1. 1.Maastricht UniversityMaastrichtThe Netherlands

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