Skip to main content
Top
Published in: Skeletal Radiology 3/2019

01-03-2019 | Scientific Article

Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity

Authors: Stijn A. Bos, Corey M. Gill, Edgar L. Martinez-Salazar, Martin Torriani, Miriam A. Bredella

Published in: Skeletal Radiology | Issue 3/2019

Login to get access

Abstract

Objective

To determine the role of brown adipose tissue (BAT) in cancer activity.

Materials and methods

The study group comprised 142 patients (121 female, 21 male; mean age, 49 ± 16 years) who underwent F18-FDG PET/CT (PET/CT) for staging or surveillance of cancer and who were BAT-positive on PET/CT. BAT volume by PET/CT, abdominal (visceral and subcutaneous) fat and paraspinous muscle cross-sectional areas (CSA) were assessed. Groups with and without active cancer on PET/CT were compared using a two-sided paired t test. Linear regression analyses between BAT and body composition parameters were performed.

Results

There were 62 patients (54 female, eight male) who had active cancer on PET/CT and 80 patients (67 female, 13 male) without active cancer. Groups were similar in age and BMI (p ≥ 0.4), abdominal fat and muscle CSA, fasting glucose, and outside temperature at time of scan (p ≥ 0.2). Patients who had active cancer on PET/CT had higher BAT volume compared to patients without active cancer (p = 0.009). In patients without active cancer, BAT was positively associated with BMI and abdominal fat depots (r = 0.46 to r = 0.59, p < 0.0001) while there were no such associations in patients with active cancer (p ≥ 0.1). No associations between BAT and age or muscle CSA were found (p ≥ 0.1).

Conclusions

BAT activity is greater in patients with active cancer compared to age-, sex-, and BMI-matched BAT-positive patients without active cancer, suggesting a possible role of BAT in cancer activity.
Appendix
Available only for authorised users
Literature
1.
go back to reference Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, et al. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 2011;71(7):2455–65.CrossRef Dirat B, Bochet L, Dabek M, Daviaud D, Dauvillier S, Majed B, et al. Cancer-associated adipocytes exhibit an activated phenotype and contribute to breast cancer invasion. Cancer Res. 2011;71(7):2455–65.CrossRef
2.
go back to reference Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" cancer cell mitochondria. Cell Metab. 2012;15(1):4–5.CrossRef Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" cancer cell mitochondria. Cell Metab. 2012;15(1):4–5.CrossRef
3.
go back to reference Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta. 2013;1831(10):1533–41.CrossRef Nieman KM, Romero IL, Van Houten B, Lengyel E. Adipose tissue and adipocytes support tumorigenesis and metastasis. Biochim Biophys Acta. 2013;1831(10):1533–41.CrossRef
4.
go back to reference Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56.CrossRef Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56.CrossRef
5.
go back to reference Cinti S. The adipose organ at a glance. Dis Model Mech. 2012;5(5):588–94.CrossRef Cinti S. The adipose organ at a glance. Dis Model Mech. 2012;5(5):588–94.CrossRef
6.
go back to reference Klopp AH, Zhang Y, Solley T, Amaya-Manzanares F, Marini F, Andreeff M, et al. Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors. Clin Cancer Res. 2011;18(3):771–82.CrossRef Klopp AH, Zhang Y, Solley T, Amaya-Manzanares F, Marini F, Andreeff M, et al. Omental adipose tissue-derived stromal cells promote vascularization and growth of endometrial tumors. Clin Cancer Res. 2011;18(3):771–82.CrossRef
7.
go back to reference Zhang Y, Daquinag A, Traktuev DO, Amaya-Manzanares F, Simmons PJ, March KL, et al. White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res. 2009;69(12):5259–66.CrossRef Zhang Y, Daquinag A, Traktuev DO, Amaya-Manzanares F, Simmons PJ, March KL, et al. White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res. 2009;69(12):5259–66.CrossRef
8.
go back to reference Smith SR, Lovejoy JC, Greenway F, Ryan D, de Jonge L, de la Bretonne J, et al. Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism. 2001;50(4):425–35.CrossRef Smith SR, Lovejoy JC, Greenway F, Ryan D, de Jonge L, de la Bretonne J, et al. Contributions of total body fat, abdominal subcutaneous adipose tissue compartments, and visceral adipose tissue to the metabolic complications of obesity. Metabolism. 2001;50(4):425–35.CrossRef
9.
go back to reference Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.CrossRef Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.CrossRef
10.
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(15):1509–17.CrossRef 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(15):1509–17.CrossRef
11.
go back to reference Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.CrossRef Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.CrossRef
12.
go back to reference Whittle AJ, Lopez M, Vidal-Puig A. Using brown adipose tissue to treat obesity—the central issue. Trends Mol Med. 2011;17(8):405–11.CrossRef Whittle AJ, Lopez M, Vidal-Puig A. Using brown adipose tissue to treat obesity—the central issue. Trends Mol Med. 2011;17(8):405–11.CrossRef
13.
go back to reference Wu C, Cheng W, Sun Y, Dang Y, Gong F, Zhu H, et al. Activating brown adipose tissue for weight loss and lowering of blood glucose levels: a microPET study using obese and diabetic model mice. PLoS One. 2014;9(12):e113742.CrossRef Wu C, Cheng W, Sun Y, Dang Y, Gong F, Zhu H, et al. Activating brown adipose tissue for weight loss and lowering of blood glucose levels: a microPET study using obese and diabetic model mice. PLoS One. 2014;9(12):e113742.CrossRef
14.
go back to reference Cao Q, Hersl J, La H, Smith M, Jenkins J, Goloubeva O, et al. A pilot study of FDG PET/CT detects a link between brown adipose tissue and breast cancer. BMC Cancer. 2014;14:126.CrossRef Cao Q, Hersl J, La H, Smith M, Jenkins J, Goloubeva O, et al. A pilot study of FDG PET/CT detects a link between brown adipose tissue and breast cancer. BMC Cancer. 2014;14:126.CrossRef
15.
go back to reference Huang YC, Chen TB, Hsu CC, Li SH, Wang PW, Lee BF, et al. The relationship between brown adipose tissue activity and neoplastic status: an (18)F-FDG PET/CT study in the tropics. Lipids Health Dis. 2011;10:238.CrossRef Huang YC, Chen TB, Hsu CC, Li SH, Wang PW, Lee BF, et al. The relationship between brown adipose tissue activity and neoplastic status: an (18)F-FDG PET/CT study in the tropics. Lipids Health Dis. 2011;10:238.CrossRef
16.
go back to reference Kir S, Spiegelman BM. Cachexia and brown fat: a burning issue in cancer. Trends Cancer. 2016;2(9):461–3.CrossRef Kir S, Spiegelman BM. Cachexia and brown fat: a burning issue in cancer. Trends Cancer. 2016;2(9):461–3.CrossRef
17.
go back to reference Lim S, Hosaka K, Nakamura M, Cao Y. Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis. Oncotarget. 2016;7(25):38282–91.CrossRef Lim S, Hosaka K, Nakamura M, Cao Y. Co-option of pre-existing vascular beds in adipose tissue controls tumor growth rates and angiogenesis. Oncotarget. 2016;7(25):38282–91.CrossRef
18.
go back to reference Jones LP, Buelto D, Tago E, Owusu-Boaitey KE. Abnormal mammary adipose tissue environment of brca1 mutant mice show a persistent deposition of highly vascularized multilocular adipocytes. J Cancer Sci Ther. 2011(Suppl 2). Jones LP, Buelto D, Tago E, Owusu-Boaitey KE. Abnormal mammary adipose tissue environment of brca1 mutant mice show a persistent deposition of highly vascularized multilocular adipocytes. J Cancer Sci Ther. 2011(Suppl 2).
19.
go back to reference Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA, et al. Brown adipose reporting criteria in imaging studies (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab. 2016;24(2):210–22.CrossRef Chen KY, Cypess AM, Laughlin MR, Haft CR, Hu HH, Bredella MA, et al. Brown adipose reporting criteria in imaging studies (BARCIST 1.0): recommendations for standardized FDG-PET/CT experiments in humans. Cell Metab. 2016;24(2):210–22.CrossRef
20.
go back to reference Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M. Imaging of brown adipose tissue: state of the art. Radiology. 2016;280(1):4–19.CrossRef Sampath SC, Sampath SC, Bredella MA, Cypess AM, Torriani M. Imaging of brown adipose tissue: state of the art. Radiology. 2016;280(1):4–19.CrossRef
21.
go back to reference Lahesmaa M, Orava J, Schalin-Jantti C, Soinio M, Hannukainen JC, Noponen T, et al. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab. 2014;99(1):E28–35.CrossRef Lahesmaa M, Orava J, Schalin-Jantti C, Soinio M, Hannukainen JC, Noponen T, et al. Hyperthyroidism increases brown fat metabolism in humans. J Clin Endocrinol Metab. 2014;99(1):E28–35.CrossRef
22.
go back to reference Gelfand MJ, O'Hara SM, Curtwright LA, Maclean JR. Pre-medication to block [(18)F] FDG uptake in the brown adipose tissue of pediatric and adolescent patients. Pediatr Radiol. 2005;35(10):984–90.CrossRef Gelfand MJ, O'Hara SM, Curtwright LA, Maclean JR. Pre-medication to block [(18)F] FDG uptake in the brown adipose tissue of pediatric and adolescent patients. Pediatr Radiol. 2005;35(10):984–90.CrossRef
23.
go back to reference Parysow O, Mollerach AM, Jager V, Racioppi S, San Roman J, Gerbaudo VH. Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans. Clin Nucl Med. 2007;32(5):351–7.CrossRef Parysow O, Mollerach AM, Jager V, Racioppi S, San Roman J, Gerbaudo VH. Low-dose oral propranolol could reduce brown adipose tissue F-18 FDG uptake in patients undergoing PET scans. Clin Nucl Med. 2007;32(5):351–7.CrossRef
24.
go back to reference Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.CrossRef Fearon K, Strasser F, Anker SD, Bosaeus I, Bruera E, Fainsinger RL, et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 2011;12(5):489–95.CrossRef
25.
go back to reference Bredella MA, Gill CM, Rosen CJ, Klibanski A, Torriani M. Positive effects of brown adipose tissue on femoral bone structure. Bone. 2014;58:55–8. Bredella MA, Gill CM, Rosen CJ, Klibanski A, Torriani M. Positive effects of brown adipose tissue on femoral bone structure. Bone. 2014;58:55–8.
26.
go back to reference Barbaras L, Tal I, Palmer MR, Parker JA, Kolodny GM. Shareware program for nuclear medicine and PET/CT PACS display and processing. AJR Am J Roentgenol. 2007;188(6):W565–8.CrossRef Barbaras L, Tal I, Palmer MR, Parker JA, Kolodny GM. Shareware program for nuclear medicine and PET/CT PACS display and processing. AJR Am J Roentgenol. 2007;188(6):W565–8.CrossRef
27.
go back to reference Shen W, Punyanitya M, Wang Z, Gallagher D, St-Onge MP, Albu J, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol. 2004;97(6):2333–8.CrossRef Shen W, Punyanitya M, Wang Z, Gallagher D, St-Onge MP, Albu J, et al. Total body skeletal muscle and adipose tissue volumes: estimation from a single abdominal cross-sectional image. J Appl Physiol. 2004;97(6):2333–8.CrossRef
28.
go back to reference Borkan GA, Gerzof SG, Robbins AH, Hults DE, Silbert CK, Silbert JE. Assessment of abdominal fat content by computed tomography. Am J Clin Nutr. 1982;36(1):172–7.CrossRef Borkan GA, Gerzof SG, Robbins AH, Hults DE, Silbert CK, Silbert JE. Assessment of abdominal fat content by computed tomography. Am J Clin Nutr. 1982;36(1):172–7.CrossRef
29.
go back to reference Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol. 1998;85(1):115–22.CrossRef Mitsiopoulos N, Baumgartner RN, Heymsfield SB, Lyons W, Gallagher D, Ross R. Cadaver validation of skeletal muscle measurement by magnetic resonance imaging and computerized tomography. J Appl Physiol. 1998;85(1):115–22.CrossRef
30.
go back to reference Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.CrossRef Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.CrossRef
31.
go back to reference Chen J. Multiple signal pathways in obesity-associated cancer. Obes Rev. 2011;12(12):1063–70.CrossRef Chen J. Multiple signal pathways in obesity-associated cancer. Obes Rev. 2011;12(12):1063–70.CrossRef
32.
go back to reference Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78.CrossRef Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78.CrossRef
33.
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(15):1500–8.CrossRef 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(15):1500–8.CrossRef
34.
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(15):1518–25.CrossRef 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(15):1518–25.CrossRef
35.
go back to reference Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci U S A. 2007;104(11):4401–6.CrossRef Timmons JA, Wennmalm K, Larsson O, Walden TB, Lassmann T, Petrovic N, et al. Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages. Proc Natl Acad Sci U S A. 2007;104(11):4401–6.CrossRef
36.
go back to reference Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab. 2010;298(6):E1244–53.CrossRef Barbatelli G, Murano I, Madsen L, Hao Q, Jimenez M, Kristiansen K, et al. The emergence of cold-induced brown adipocytes in mouse white fat depots is determined predominantly by white to brown adipocyte transdifferentiation. Am J Physiol Endocrinol Metab. 2010;298(6):E1244–53.CrossRef
37.
go back to reference Walden TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J. Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues. Am J Physiol Endocrinol Metab. 2012;302(1):E19–31.CrossRef Walden TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J. Recruited vs. nonrecruited molecular signatures of brown, "brite," and white adipose tissues. Am J Physiol Endocrinol Metab. 2012;302(1):E19–31.CrossRef
38.
go back to reference Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–8.CrossRef Bostrom P, Wu J, Jedrychowski MP, Korde A, Ye L, Lo JC, et al. A PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat and thermogenesis. Nature. 2012;481(7382):463–8.CrossRef
39.
go back to reference Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med. 2013;19(5):635–9.CrossRef Cypess AM, White AP, Vernochet C, Schulz TJ, Xue R, Sass CA, et al. Anatomical localization, gene expression profiling and functional characterization of adult human neck brown fat. Nat Med. 2013;19(5):635–9.CrossRef
40.
go back to reference Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366–76.CrossRef Wu J, Bostrom P, Sparks LM, Ye L, Choi JH, Giang AH, et al. Beige adipocytes are a distinct type of thermogenic fat cell in mouse and human. Cell. 2012;150(2):366–76.CrossRef
41.
go back to reference Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, et al. 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. 2011;96(1):192–9.CrossRef Ouellet V, Routhier-Labadie A, Bellemare W, Lakhal-Chaieb L, Turcotte E, Carpentier AC, et al. 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. 2011;96(1):192–9.CrossRef
42.
go back to reference Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.CrossRef Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.CrossRef
43.
go back to reference Tsoli M, Moore M, Burg D, Painter A, Taylor R, Lockie SH, et al. Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice. Cancer Res. 2012;72(17):4372–82.CrossRef Tsoli M, Moore M, Burg D, Painter A, Taylor R, Lockie SH, et al. Activation of thermogenesis in brown adipose tissue and dysregulated lipid metabolism associated with cancer cachexia in mice. Cancer Res. 2012;72(17):4372–82.CrossRef
44.
go back to reference Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 2014;20(3):433–47.CrossRef Petruzzelli M, Schweiger M, Schreiber R, Campos-Olivas R, Tsoli M, Allen J, et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 2014;20(3):433–47.CrossRef
45.
go back to reference Cypess AM, Haft CR, Laughlin MR, Hu HH. Brown fat in humans: consensus points and experimental guidelines. Cell Metab. 2014;20(3):408–15.CrossRef Cypess AM, Haft CR, Laughlin MR, Hu HH. Brown fat in humans: consensus points and experimental guidelines. Cell Metab. 2014;20(3):408–15.CrossRef
Metadata
Title
Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity
Authors
Stijn A. Bos
Corey M. Gill
Edgar L. Martinez-Salazar
Martin Torriani
Miriam A. Bredella
Publication date
01-03-2019
Publisher
Springer Berlin Heidelberg
Published in
Skeletal Radiology / Issue 3/2019
Print ISSN: 0364-2348
Electronic ISSN: 1432-2161
DOI
https://doi.org/10.1007/s00256-018-3046-x

Other articles of this Issue 3/2019

Skeletal Radiology 3/2019 Go to the issue