Skip to main content

Advertisement

SpringerLink
Log in

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

  • Scientific Article
  • Published:
Skeletal Radiology Aims and scope Submit manuscript

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.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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.

    Article  CAS  Google Scholar 

  2. Martinez-Outschoorn UE, Sotgia F, Lisanti MP. Power surge: supporting cells "fuel" cancer cell mitochondria. Cell Metab. 2012;15(1):4–5.

    Article  CAS  Google Scholar 

  3. 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.

    Article  CAS  Google Scholar 

  4. Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89(6):2548–56.

    Article  CAS  Google Scholar 

  5. Cinti S. The adipose organ at a glance. Dis Model Mech. 2012;5(5):588–94.

    Article  CAS  Google Scholar 

  6. 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.

    Article  Google Scholar 

  7. 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.

    Article  CAS  Google Scholar 

  8. 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.

    Article  CAS  Google Scholar 

  9. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev. 2000;21(6):697–738.

    Article  CAS  Google Scholar 

  10. 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.

    Article  CAS  Google Scholar 

  11. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.

    Article  CAS  Google Scholar 

  12. 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.

    Article  Google Scholar 

  13. 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.

    Article  Google Scholar 

  14. 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.

    Article  Google Scholar 

  15. 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.

    Article  CAS  Google Scholar 

  16. Kir S, Spiegelman BM. Cachexia and brown fat: a burning issue in cancer. Trends Cancer. 2016;2(9):461–3.

    Article  Google Scholar 

  17. 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.

    Article  Google Scholar 

  18. 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. 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.

    Article  CAS  Google Scholar 

  20. 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.

    Article  Google Scholar 

  21. 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.

    Article  Google Scholar 

  22. 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.

    Article  Google Scholar 

  23. 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.

    Article  Google Scholar 

  24. 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.

    Article  Google Scholar 

  25. 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. 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.

    Article  Google Scholar 

  27. 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.

    Article  Google Scholar 

  28. 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.

    Article  CAS  Google Scholar 

  29. 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.

    Article  CAS  Google Scholar 

  30. 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.

    Article  Google Scholar 

  31. Chen J. Multiple signal pathways in obesity-associated cancer. Obes Rev. 2011;12(12):1063–70.

    Article  Google Scholar 

  32. 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.

    Article  Google Scholar 

  33. 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.

    Article  Google Scholar 

  34. 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.

    Article  CAS  Google Scholar 

  35. 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.

    Article  CAS  Google Scholar 

  36. 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.

    Article  CAS  Google Scholar 

  37. 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.

    Article  CAS  Google Scholar 

  38. 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.

    Article  Google Scholar 

  39. 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.

    Article  CAS  Google Scholar 

  40. 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.

    Article  CAS  Google Scholar 

  41. 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.

    Article  CAS  Google Scholar 

  42. Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.

    Article  CAS  Google Scholar 

  43. 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.

    Article  CAS  Google Scholar 

  44. 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.

    Article  CAS  Google Scholar 

  45. 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  Google Scholar 

Download references

Funding

This study was supported by NIH grants K24 DK-109940 and P30DK040561.

Author information

Author notes

  1. Stijn A. Bos

    Present address: Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands

  2. Corey M. Gill

    Present address: Department of Medicine, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave, New York, NY, 10029, USA

Authors and Affiliations

  1. Division of Musculoskeletal Imaging and Intervention, Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Yawkey 6E, 55 Fruit Street, Boston, MA, 02114, USA

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

Authors
  1. Stijn A. Bos
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Corey M. Gill
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edgar L. Martinez-Salazar
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Martin Torriani
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Miriam A. Bredella
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Miriam A. Bredella.

Ethics declarations

Conflict of interest

The authors declare that they have no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was waived for this retrospective study.

Electronic supplementary material

Supplementary Figure 1

Quantification of brown adipose tissue in regions of interest (green outline) in images obtained with positron-emission tomography (PET) (A) and CT (B). (PNG 524 kb)

High-resolution image (TIF 8260 kb)

Supplementary Figure 2

Quantification of abdominal total adipose tissue (A), visceral adipose tissue (B), subcutaneous adipose tissue (C), and paraspinal muscle (D) on axial non-contrast CT using semiautomated methods. (PNG 620 kb)

(PNG 1356 kb)

(PNG 914 kb)

(PNG 1081 kb)

High-resolution image (TIF 4870 kb)

High-resolution image (TIF 14244 kb)

High-resolution image (TIF 9262 kb)

High-resolution image (TIF 10222 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bos, S.A., Gill, C.M., Martinez-Salazar, E.L. et al. Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity. Skeletal Radiol 48, 413–419 (2019). https://doi.org/10.1007/s00256-018-3046-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00256-018-3046-x

Keywords

Search

Navigation