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Published in: European Journal of Nuclear Medicine and Molecular Imaging 10/2016

Open Access 01-09-2016 | Original Article

Human brown adipose tissue [15O]O2 PET imaging in the presence and absence of cold stimulus

Authors: Mueez u Din, Juho Raiko, Teemu Saari, Nobu Kudomi, Tuula Tolvanen, Vesa Oikonen, Jarmo Teuho, Hannu T Sipilä, Nina Savisto, Riitta Parkkola, Pirjo Nuutila, Kirsi A. Virtanen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 10/2016

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Abstract

Purpose

Brown adipose tissue (BAT) is considered a potential target for combatting obesity, as it produces heat instead of ATP in cellular respiration due to uncoupling protein-1 (UCP-1) in mitochondria. However, BAT-specific thermogenic capacity, in comparison to whole-body thermogenesis during cold stimulus, is still controversial. In our present study, we aimed to determine human BAT oxygen consumption with [15O]O2 positron emission tomography (PET) imaging. Further, we explored whether BAT-specific energy expenditure (EE) is associated with BAT blood flow, non-esterified fatty acid (NEFA) uptake, and whole-body EE.

Methods

Seven healthy study subjects were studied at two different scanning sessions, 1) at room temperature (RT) and 2) with acute cold exposure. Radiotracers [15O]O2, [15O]H2O, and [18F]FTHA were given for the measurements of BAT oxygen consumption, blood flow, and NEFA uptake, respectively, with PET-CT. Indirect calorimetry was performed to assess differences in whole-body EE between RT and cold.

Results

BAT-specific EE and oxygen consumption was higher during cold stimulus (approx. 50 %); similarly, whole-body EE was higher during cold stimulus (range 2–47 %). However, there was no association in BAT-specific EE and whole-body EE. BAT-specific EE was found to be a minor contributor in cold induced whole-body thermogenesis (almost 1 % of total whole-body elevation in EE). Certain deep muscles in the cervico-thoracic region made a major contribution to this cold-induced thermogenesis (CIT) without any visual signs or individual perception of shivering. Moreover, BAT-specific EE associated with BAT blood flow and NEFA uptake both at RT and during cold stimulus.

Conclusion

Our study suggests that BAT is a minor and deep muscles are a major contributor to CIT. In BAT, both in RT and during cold, cellular respiration is linked with circulatory NEFA uptake.
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Literature
1.
go back to reference Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta. 2001;1504:82–106.CrossRefPubMed Nedergaard J, Golozoubova V, Matthias A, Asadi A, Jacobsson A, Cannon B. UCP1: the only protein able to mediate adaptive non-shivering thermogenesis and metabolic inefficiency. Biochim Biophys Acta. 2001;1504:82–106.CrossRefPubMed
2.
go back to reference Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.CrossRefPubMedPubMedCentral Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360:1509–17.CrossRefPubMedPubMedCentral
3.
go back to reference van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–8.CrossRefPubMed van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360:1500–8.CrossRefPubMed
4.
go back to reference Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360:1518–25.CrossRefPubMed Virtanen KA, Lidell ME, Orava J, Heglind M, Westergren R, Niemi T, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360:1518–25.CrossRefPubMed
5.
go back to reference Cinti S. The role of brown adipose tissue in human obesity. Nutr Metab Cardiovasc Dis. 2006;16:569–74.CrossRefPubMed Cinti S. The role of brown adipose tissue in human obesity. Nutr Metab Cardiovasc Dis. 2006;16:569–74.CrossRefPubMed
6.
go back to reference Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat ("USA-Fat"): description on 18F-FDG PET/CT. J Nucl Med. 2003;44:170–6.PubMed Cohade C, Osman M, Pannu HK, Wahl RL. Uptake in supraclavicular area fat ("USA-Fat"): description on 18F-FDG PET/CT. J Nucl Med. 2003;44:170–6.PubMed
7.
go back to reference Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011;14:272–9.CrossRefPubMed Orava J, Nuutila P, Lidell ME, Oikonen V, Noponen T, Viljanen T, et al. Different metabolic responses of human brown adipose tissue to activation by cold and insulin. Cell Metab. 2011;14:272–9.CrossRefPubMed
8.
go back to reference Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58:1526–31.CrossRefPubMedPubMedCentral Saito M, Okamatsu-Ogura Y, Matsushita M, Watanabe K, Yoneshiro T, Nio-Kobayashi J, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58:1526–31.CrossRefPubMedPubMedCentral
9.
go back to reference Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y, et al. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring). 2011;19:13–6.CrossRef Yoneshiro T, Aita S, Matsushita M, Kameya T, Nakada K, Kawai Y, et al. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring). 2011;19:13–6.CrossRef
10.
go back to reference Ma SW, Foster DO. Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo. Can J Physiol Pharmacol. 1986;64:609–14.CrossRefPubMed Ma SW, Foster DO. Uptake of glucose and release of fatty acids and glycerol by rat brown adipose tissue in vivo. Can J Physiol Pharmacol. 1986;64:609–14.CrossRefPubMed
11.
go back to reference Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J, Granneman JG. 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med. 2013;54:523–31.CrossRefPubMed Muzik O, Mangner TJ, Leonard WR, Kumar A, Janisse J, Granneman JG. 15O PET measurement of blood flow and oxygen consumption in cold-activated human brown fat. J Nucl Med. 2013;54:523–31.CrossRefPubMed
13.
go back to reference DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214–23.PubMed DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol. 1979;237:E214–23.PubMed
14.
go back to reference Saari T, Raiko J, Niemi T, Taittonen M, Laine J, Savisto N, Haaparanta-Solin M, Nuutila P, Virtanen KT. Impaired brown adipose tissue fatty acid metabolism in obese subjects. Diabetologia. 2014;57[Suppl1]:S14–S14. Saari T, Raiko J, Niemi T, Taittonen M, Laine J, Savisto N, Haaparanta-Solin M, Nuutila P, Virtanen KT. Impaired brown adipose tissue fatty acid metabolism in obese subjects. Diabetologia. 2014;57[Suppl1]:S14–S14.
15.
go back to reference Iida H, Jones T, Miura S. Modeling approach to eliminate the need to separate arterial plasma in oxygen-15 inhalation positron emission tomography. J Nucl Med. 1993;34:1333–40.PubMed Iida H, Jones T, Miura S. Modeling approach to eliminate the need to separate arterial plasma in oxygen-15 inhalation positron emission tomography. J Nucl Med. 1993;34:1333–40.PubMed
16.
go back to reference Kudomi N, Hirano Y, Koshino K, Hayashi T, Watabe H, Fukushima K, et al. Rapid quantitative CBF and CMRO(2) measurements from a single PET scan with sequential administration of dual (15)O-labeled tracers. J Cereb Blood Flow Metab. 2013;33:440–8.CrossRefPubMed Kudomi N, Hirano Y, Koshino K, Hayashi T, Watabe H, Fukushima K, et al. Rapid quantitative CBF and CMRO(2) measurements from a single PET scan with sequential administration of dual (15)O-labeled tracers. J Cereb Blood Flow Metab. 2013;33:440–8.CrossRefPubMed
17.
go back to reference Nuutila P, Peltoniemi P, Oikonen V, Larmola K, Kemppainen J, Takala T, et al. Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. Diabetes. 2000;49:1084–91.CrossRefPubMed Nuutila P, Peltoniemi P, Oikonen V, Larmola K, Kemppainen J, Takala T, et al. Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. Diabetes. 2000;49:1084–91.CrossRefPubMed
18.
go back to reference Oikonen V, Nuutila P, Sipilä H, Tolvanen T, Peltoniemi P, Ruotsalainen U. Quantification of oxygen consumption in skeletal muscle with PET and oxygen-15 bolus. Eur J Nucl Med. 1998;25:1151. Oikonen V, Nuutila P, Sipilä H, Tolvanen T, Peltoniemi P, Ruotsalainen U. Quantification of oxygen consumption in skeletal muscle with PET and oxygen-15 bolus. Eur J Nucl Med. 1998;25:1151.
21.
go back to reference Leonard WR. Measuring human energy expenditure and metabolic function: basic principles and methods. J Anthropol Sci. 2010;88:221–30.PubMed Leonard WR. Measuring human energy expenditure and metabolic function: basic principles and methods. J Anthropol Sci. 2010;88:221–30.PubMed
22.
go back to reference Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98:E1218–23.CrossRefPubMedPubMedCentral Chen KY, Brychta RJ, Linderman JD, Smith S, Courville A, Dieckmann W, et al. Brown fat activation mediates cold-induced thermogenesis in adult humans in response to a mild decrease in ambient temperature. J Clin Endocrinol Metab. 2013;98:E1218–23.CrossRefPubMedPubMedCentral
23.
go back to reference Klein LJ, Visser FC, Knaapen P, Peters JH, Teule GJ, Visser CA, et al. Carbon-11 acetate as a tracer of myocardial oxygen consumption. Eur J Nucl Med. 2001;28:651–68.CrossRefPubMed Klein LJ, Visser FC, Knaapen P, Peters JH, Teule GJ, Visser CA, et al. Carbon-11 acetate as a tracer of myocardial oxygen consumption. Eur J Nucl Med. 2001;28:651–68.CrossRefPubMed
24.
go back to reference Blondin DP, Labbe SM, Phoenix S, Guerin B, Turcotte EE, Richard D, et al. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol. 2015;593:701–14.CrossRefPubMed Blondin DP, Labbe SM, Phoenix S, Guerin B, Turcotte EE, Richard D, et al. Contributions of white and brown adipose tissues and skeletal muscles to acute cold-induced metabolic responses in healthy men. J Physiol. 2015;593:701–14.CrossRefPubMed
25.
go back to reference Stocks JM, Taylor NA, Tipton MJ, Greenleaf JE. Human physiological responses to cold exposure. Aviat Space Environ Med. 2004;75:444–57.PubMed Stocks JM, Taylor NA, Tipton MJ, Greenleaf JE. Human physiological responses to cold exposure. Aviat Space Environ Med. 2004;75:444–57.PubMed
26.
go back to reference Geerling JJ, Boon MR, Kooijman S, Parlevliet ET, Havekes LM, Romijn JA, et al. Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies. J Lipid Res. 2014;55:180–9.CrossRefPubMedPubMedCentral Geerling JJ, Boon MR, Kooijman S, Parlevliet ET, Havekes LM, Romijn JA, et al. Sympathetic nervous system control of triglyceride metabolism: novel concepts derived from recent studies. J Lipid Res. 2014;55:180–9.CrossRefPubMedPubMedCentral
27.
go back to reference Simonyan RA, Jimenez M, Ceddia RB, Giacobino JP, Muzzin P, Skulachev VP. Cold-induced changes in the energy coupling and the UCP3 level in rodent skeletal muscles. Biochim Biophys Acta. 2001;1505:271–9.CrossRefPubMed Simonyan RA, Jimenez M, Ceddia RB, Giacobino JP, Muzzin P, Skulachev VP. Cold-induced changes in the energy coupling and the UCP3 level in rodent skeletal muscles. Biochim Biophys Acta. 2001;1505:271–9.CrossRefPubMed
28.
go back to reference Mollica MP, Lionetti L, Crescenzo R, Tasso R, Barletta A, Liverini G, et al. Cold exposure differently influences mitochondrial energy efficiency in rat liver and skeletal muscle. FEBS Lett. 2005;579:1978–82.CrossRefPubMed Mollica MP, Lionetti L, Crescenzo R, Tasso R, Barletta A, Liverini G, et al. Cold exposure differently influences mitochondrial energy efficiency in rat liver and skeletal muscle. FEBS Lett. 2005;579:1978–82.CrossRefPubMed
29.
go back to reference Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt WD. Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis. PLoS ONE. 2008;3, e1777.CrossRefPubMedPubMedCentral Wijers SL, Schrauwen P, Saris WH, van Marken Lichtenbelt WD. Human skeletal muscle mitochondrial uncoupling is associated with cold induced adaptive thermogenesis. PLoS ONE. 2008;3, e1777.CrossRefPubMedPubMedCentral
30.
go back to reference Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, Haman F, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012;122:545–52.CrossRefPubMedPubMedCentral Ouellet V, Labbe SM, Blondin DP, Phoenix S, Guerin B, Haman F, et al. Brown adipose tissue oxidative metabolism contributes to energy expenditure during acute cold exposure in humans. J Clin Invest. 2012;122:545–52.CrossRefPubMedPubMedCentral
31.
go back to reference Orava J, Nuutila P, Noponen T, Parkkola R, Viljanen T, Enerback S, et al. Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans. Obesity (Silver Spring). 2013;21:2279–87.CrossRef Orava J, Nuutila P, Noponen T, Parkkola R, Viljanen T, Enerback S, et al. Blunted metabolic responses to cold and insulin stimulation in brown adipose tissue of obese humans. Obesity (Silver Spring). 2013;21:2279–87.CrossRef
Metadata
Title
Human brown adipose tissue [15O]O2 PET imaging in the presence and absence of cold stimulus
Authors
Mueez u Din
Juho Raiko
Teemu Saari
Nobu Kudomi
Tuula Tolvanen
Vesa Oikonen
Jarmo Teuho
Hannu T Sipilä
Nina Savisto
Riitta Parkkola
Pirjo Nuutila
Kirsi A. Virtanen
Publication date
01-09-2016
Publisher
Springer Berlin Heidelberg
Published in
European Journal of Nuclear Medicine and Molecular Imaging / Issue 10/2016
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI
https://doi.org/10.1007/s00259-016-3364-y

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