The purpose of our study was to determine the role of brown adipose tissue (BAT) in cancer progression.
Materials and methods
Our study was approved by our institutional review board and Health Insurance Portability and Accountability Act–compliant. Our study group comprised 132 cancer patients (116 f, 16 m; mean age 50 ± 16 years) who underwent F18-FDG PET/CT per standard clinical protocol, for staging or surveillance of cancer. We included patients who were BAT-positive on PET/CT and had clinical follow-up data available for at least 12 months or until tumor recurrence or tumor-related death, whichever occurred first. BAT volume by PET/CT was quantified by PET-CT Viewer shareware. Clinical information including tumor type, tumor recurrence, survival, and outside temperature at time of scan were recorded. Cox proportional hazard models were used to determine longitudinal associations between BAT volume and tumor recurrence/mortality.
There were 55 tumor recurrences/tumor-related deaths over a median follow-up period of 71 (33; 110 interquartile range) months. Higher BAT volume was associated with an increased likelihood of tumor recurrence/tumor-associated mortality after adjustment for covariates (p = 0.03).
BAT volume, assessed using routine PET/CT, is a predictor of tumor recurrence/mortality in patients with cancer, independent of other factors that can influence BAT activity, such as sex, age, BMI, or tumor type.
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Dittmer J, Leyh B. Paracrine effects of stem cells in wound healing and cancer progression (review). Int J Oncol. 2014;44(6):1789–98.
Kaplan RN, Riba RD, Zacharoulis S, Bramley AH, Vincent L, Costa C, et al. VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature. 2005;438(7069):820–7.
Peinado H, Zhang H, Matei IR, Costa-Silva B, Hoshino A, Rodrigues G, et al. Pre-metastatic niches: organ-specific homes for metastases. Nat Rev Cancer. 2017;17(5):302–17.
Himbert C, Delphan M, Scherer D, Bowers LW, Hursting S, Ulrich CM. Signals from the adipose microenvironment and the obesity-cancer link-a systematic review. Cancer Prev Res (Phila). 2017;10(9):494–506.
Nieman KM, Kenny HA, Penicka CV, Ladanyi A, Buell-Gutbrod R, Zillhardt MR, et al. Adipocytes promote ovarian cancer metastasis and provide energy for rapid tumor growth. Nat Med. 2011;17(11):1498–503.
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.
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.
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.
Bos SA, Gill CM, Martinez-Salazar EL, Torriani M, Bredella MA. Preliminary investigation of brown adipose tissue assessed by PET/CT and cancer activity. Skelet Radiol. 2019;48(3):413–9.
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.
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.
Kir S, Spiegelman BM. Cachexia and brown fat: a burning issue in cancer. Trends Cancer. 2016;2(9):461–3.
Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev. 2004;84(1):277–359.
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.
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.
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.
Lim S, Honek J, Xue Y, Seki T, Cao Z, Andersson P, et al. Cold-induced activation of brown adipose tissue and adipose angiogenesis in mice. Nat Protoc. 2012;7(3):606–15.
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.
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.
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.
Grignol VP, Smith AD, Shlapak D, Zhang X, Del Campo SM, Carson WE. Increased visceral to subcutaneous fat ratio is associated with decreased overall survival in patients with metastatic melanoma receiving anti-angiogenic therapy. Surg Oncol. 2015;24(4):353–8.
Shin DY, Kim A, Byun BH, Moon H, Kim S, Ko YJ, et al. Visceral adipose tissue is prognostic for survival of diffuse large B cell lymphoma treated with frontline R-CHOP. Ann Hematol. 2016;95(3):409–16.
Veld J, O’Donnell EK, Reagan MR, Yee AJ, Torriani M, Rosen CJ, et al. Abdominal adipose tissue in MGUS and multiple myeloma. Skelet Radiol. 2016;45(9):1277–83.
Veld J, Vossen JA, De Amorim Bernstein K, Halpern EF, Torriani M, Bredella MA. Adipose tissue and muscle attenuation as novel biomarkers predicting mortality in patients with extremity sarcomas. Eur Radiol. 2016;26:4649–55.
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.
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.
Cronin CG, Prakash P, Daniels GH, Boland GW, Kalra MK, Halpern EF, et al. Brown fat at PET/CT: correlation with patient characteristics. Radiology. 2012;263(3):836–42.
Steinberg JD, Vogel W, Vegt E. Factors influencing brown fat activation in FDG PET/CT: a retrospective analysis of 15,000+ cases. Br J Radiol. 2017;90(1075):20170093.
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.
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; 8(Suppl 2). pii:004. https://phstwlp2.partners.org:2052/pmc/articles/PMC3851023/
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.
Argiles JM, Busquets S, Stemmler B, Lopez-Soriano FJ. Cancer cachexia: understanding the molecular basis. Nat Rev Cancer. 2014;14(11):754–62.
Dalal S. Lipid metabolism in cancer cachexia. Ann Palliat Med. 2019;8(1):13–23.
Cypess AM, Haft CR, Laughlin MR, Hu HH. Brown fat in humans: consensus points and experimental guidelines. Cell Metab. 2014;20(3):408–15.
This study was supported by NIH grants K24 DK-109940 and P30DK040561.
Conflict of interest
The authors declare that they have no conflict of interest.
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 was waived for this retrospective study.
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Chu, K., Bos, S.A., Gill, C.M. et al. Brown adipose tissue and cancer progression. Skeletal Radiol 49, 635–639 (2020). https://doi.org/10.1007/s00256-019-03322-w
- FDG PET/CT
- Brown adipose tissue (BAT)
- Body composition
- Tumor recurrence