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Positron-Emission Tomography and Computed Tomography Measurement of Brown Fat Thermal Activation: Key Tools for Developing Novel Pharmacotherapeutics for Obesity and Diabetes

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Translational Research Methods for Diabetes, Obesity and Cardiometabolic Drug Development

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Abstract

Unlike white adipose tissue, brown adipose tissue is a heat-generating fat that burns energy and may have beneficial effects on obesity. This chapter reviews computed tomography and fluorodeoxyglucose positron-emission tomography studies of adipose tissue type, volume, and activation. We present imaging data on a group of insulin-resistant subjects (HOMA = 5.2, SD = 2.5) and overweight healthy volunteers with fluorodeoxyglucose positron-emission tomography and x-ray computed tomography (FDG-PET/CT) of the thorax (C6–T8) to assess the glucose metabolic rate of brown and white fat. Subjects were exposed to a 90-min period of either cold (67–68 °F) or warm (72–73 °F) temperature on separate days. Metabolic rate was quantified using aortic uptake PET values and the PMOD software. A higher cold than warm glucose metabolic rate (GMR) was observed to the greatest extent in the −120 to −80 and −80 to −40 Hounsfield bands of thoracic levels consistent with earlier reports of brown fat metabolic rate sensitivity to thermal exposure. Additionally, FDG-PET may prove sensitive enough to detect metabolic effects of therapeutic interventions on functional brown fat volume and activity.

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References

  1. Wilson JP, Kanaya AM, Fan B, Shepherd JA. Ratio of trunk to leg volume as a new body shape metric for diabetes and mortality. PLoS One. 2013;8(7):e68716. PubMed PMID: 23874736, Pubmed Central PMCID: 3707853.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. Kuk JL, Church TS, Blair SN, Ross R. Does measurement site for visceral and abdominal subcutaneous adipose tissue alter associations with the metabolic syndrome? Diabetes Care. 2006;29(3):679–84. PubMed PMID: 16505526.

    Article  PubMed  Google Scholar 

  3. Brown RE, Kuk JL, Lee S. Measurement site influences abdominal subcutaneous and visceral adipose tissue in obese adolescents before and after exercise. Pediatr Obes. 2014. PubMed PMID: 24729534.

    Google Scholar 

  4. Schulz TJ, Tseng YH. Brown adipose tissue: development, metabolism and beyond. Biochem J. 2013;453(2):167–78. PubMed PMID: 23805974, Pubmed Central PMCID: 3887508.

    Article  CAS  PubMed  Google Scholar 

  5. Arch JR. Thermogenesis and related metabolic targets in anti-diabetic therapy. Handb Exp Pharmacol. 2011;203:201–55. PubMed PMID: 21484574.

    Article  CAS  PubMed  Google Scholar 

  6. Arch JR, Trayhurn P. Detection of thermogenesis in rodents in response to anti-obesity drugs and genetic modification. Front Physiol. 2013;4:64. PubMed PMID: 23580228, Pubmed Central PMCID: 3619105.

    Article  PubMed Central  PubMed  Google Scholar 

  7. Clapham JC, Arch JR. Targeting thermogenesis and related pathways in anti-obesity drug discovery. Pharmacol Ther. 2011;131(3):295–308. PubMed PMID: 21514319.

    Article  CAS  PubMed  Google Scholar 

  8. Peirce V, Vidal-Puig A. Regulation of glucose homoeostasis by brown adipose tissue. Lancet Diabetes Endocrinol. 2013;1(4):353–60. PubMed PMID: 24622420.

    Article  CAS  PubMed  Google Scholar 

  9. 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(2):545–52. PubMed PMID: 22269323, Pubmed Central PMCID: 3266793.

    Article  PubMed Central  PubMed  Google Scholar 

  10. Cypess AM, Kahn CR. The role and importance of brown adipose tissue in energy homeostasis. Curr Opin Pediatr. 2010;22(4):478–84. PubMed PMID: 20489634, Pubmed Central PMCID: 3593062.

    Article  PubMed Central  PubMed  Google Scholar 

  11. Sims EA. Storage and expenditure of energy in obesity and their implications for management. Med Clin North Am. 1989;73(1):97–110. PubMed PMID: 2643011.

    CAS  PubMed  Google Scholar 

  12. Tupone D, Madden CJ, Morrison SF. Autonomic regulation of brown adipose tissue thermogenesis in health and disease: potential clinical applications for altering BAT thermogenesis. Front Neurosci. 2014;8:14. PubMed PMID: 24570653, Pubmed Central PMCID: 3916784.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Mirbolooki MR, Constantinescu CC, Pan ML, Mukherjee J. Quantitative assessment of brown adipose tissue metabolic activity and volume using 18F-FDG PET/CT and β3-adrenergic receptor activation. EJNMMI Res. 2011;1(1):30. PubMed PMID: 22214183, Pubmed Central PMCID: 3250993.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Mirbolooki MR, Constantinescu CC, Pan ML, Mukherjee J. Targeting presynaptic norepinephrine transporter in brown adipose tissue: a novel imaging approach and potential treatment for diabetes and obesity. Synapse. 2013;67(2):79–93. PubMed PMID: 23080264, Pubmed Central PMCID: 3808851.

    Article  CAS  PubMed  Google Scholar 

  15. Mirbolooki MR, Upadhyay SK, Constantinescu CC, Pan ML, Mukherjee J. Adrenergic pathway activation enhances brown adipose tissue metabolism: a [(1)(8)F]FDG PET/CT study in mice. Nucl Med Biol. 2014;41(1):10–6. PubMed PMID: 24090673, Pubmed Central PMCID: 3840120.

    Article  CAS  PubMed  Google Scholar 

  16. Lidell ME, Betz MJ, Dahlqvist Leinhard O, Heglind M, Elander L, Slawik M, et al. Evidence for two types of brown adipose tissue in humans. Nat Med. 2013;19(5):631–4. PubMed PMID: 23603813.

    Article  CAS  PubMed  Google Scholar 

  17. Lidell ME, Betz MJ, Enerback S. Two types of brown adipose tissue in humans. Adipocyte. 2014;3(1):63–6. PubMed PMID: 24575372, Pubmed Central PMCID: 3917936.

    Article  PubMed Central  PubMed  Google Scholar 

  18. 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(2):272–9. PubMed PMID: 21803297.

    Article  CAS  PubMed  Google Scholar 

  19. 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. 2013;21(11):2279–87. PubMed PMID: 23554353.

    Article  CAS  PubMed  Google Scholar 

  20. Enerback S. Brown adipose tissue in humans. Int J Obes. 2010;34 Suppl 1:S43–6. PubMed PMID: 20935666.

    Article  Google Scholar 

  21. Johnstone EC, Crow TJ, Frith CD, Husband J, Kreel L. Cerebral ventricular size and cognitive impairment in chronic schizophrenia. Lancet. 1976;2(7992):924–6. PubMed PMID: 62160.

    Article  CAS  PubMed  Google Scholar 

  22. Raju TN. The Nobel chronicles. 1979: Allan MacLeod Cormack (b 1924); and Sir Godfrey Newbold Hounsfield (b 1919). Lancet. 1999;354(9190):1653.

    Article  CAS  PubMed  Google Scholar 

  23. Jernigan TL, Zatz LM, Naeser MA. Semiautomated methods for quantitating CSF volume on cranial computed tomography. Radiology. 1979;132(2):463–6. PubMed PMID: 461809.

    Article  CAS  PubMed  Google Scholar 

  24. Heymsfield SB, Adamek M, Gonzalez MC, Jia G, Thomas DM. Assessing skeletal muscle mass: historical overview and state of the art. J Cachex Sarcopenia Muscle. 2014;5:9–18. PubMed PMID: 24532493.

    Article  Google Scholar 

  25. Bulcke JA, Termote JL, Palmers Y, Crolla D. Computed tomography of the human skeletal muscular system. Neuroradiology. 1979;17(3):127–36. PubMed PMID: 450236.

    CAS  PubMed  Google Scholar 

  26. Haggmark T, Jansson E, Svane B. Cross-sectional area of the thigh muscle in man measured by computed tomography. Scand J Clin Lab Invest. 1978;38(4):355–60. PubMed PMID: 684368.

    Article  CAS  PubMed  Google Scholar 

  27. Buchsbaum R. Size of explant and volume of medium in tissue cultures [Ph.D.]. Chicago: The University of Chicago; 1932.

    Google Scholar 

  28. Pasanisi F, Pace L, Fonti R, Marra M, Sgambati D, De Caprio C, et al. Evidence of brown fat activity in constitutional leanness. J Clin Endocrinol Metab. 2013;98(3):1214–8. PubMed PMID: 23393181.

    Article  CAS  PubMed  Google Scholar 

  29. 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(7):1526–31. PubMed PMID: 19401428, Pubmed Central PMCID: 2699872.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  30. 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. PubMed PMID: 20943785.

    Article  CAS  PubMed  Google Scholar 

  31. 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. PubMed PMID: 7091027.

    CAS  PubMed  Google Scholar 

  32. Grauer WO, Moss AA, Cann CE, Goldberg HI. Quantification of body fat distribution in the abdomen using computed tomography. Am J Clin Nutr. 1984;39(4):631–7. PubMed PMID: 6711470.

    CAS  PubMed  Google Scholar 

  33. 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(2):170–6. PubMed PMID: 12571205.

    CAS  PubMed  Google Scholar 

  34. 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. PubMed PMID: 19357406, Pubmed Central PMCID: 2859951.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Blondin DP, Labbe SM, Christian Tingelstad H, Noll C, Kunach M, Phoenix S, et al. Increased brown adipose tissue oxidative capacity in cold-acclimated humans. J Clin Endocrinol Metab. 2014;99:E438–46. jc20133901. PubMed PMID: 24423363.

    CAS  PubMed Central  PubMed  Google Scholar 

  36. Baba S, Jacene HA, Engles JM, Honda H, Wahl RL. CT Hounsfield units of brown adipose tissue increase with activation: preclinical and clinical studies. J Nucl Med. 2010;51(2):246–50. PubMed PMID: 20124047.

    Article  PubMed  Google Scholar 

  37. Hu HH, Chung SA, Nayak KS, Jackson HA, Gilsanz V. Differential computed tomographic attenuation of metabolically active and inactive adipose tissues: preliminary findings. J Comput Assist Tomogr. 2011;35(1):65–71. PubMed PMID: 21245691. Pubmed Central PMCID: 3074500.

    Article  PubMed Central  PubMed  Google Scholar 

  38. 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. PubMed PMID: 19357407.

    Article  CAS  PubMed  Google Scholar 

  39. Virtanen KA, Peltoniemi P, Marjamaki P, Asola M, Strindberg L, Parkkola R, et al. Human adipose tissue glucose uptake determined using [(18)F]-fluoro-deoxy-glucose ([(18)F]FDG) and PET in combination with microdialysis. Diabetologia. 2001;44(12):2171–9. PubMed PMID: 11793018.

    Article  CAS  PubMed  Google Scholar 

  40. Yoneshiro T, Aita S, Matsushita M, Okamatsu-Ogura Y, Kameya T, Kawai Y, et al. Age-related decrease in cold-activated brown adipose tissue and accumulation of body fat in healthy humans. Obesity. 2011;19(9):1755–60. PubMed PMID: 21566561.

    Article  PubMed  Google Scholar 

  41. Pfannenberg C, Werner MK, Ripkens S, Stef I, Deckert A, Schmadl M, et al. Impact of age on the relationships of brown adipose tissue with sex and adiposity in humans. Diabetes. 2010;59(7):1789–93. PubMed PMID: 20357363, Pubmed Central PMCID: 2889780.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  42. Sachpekidis C, Roumia S, Schwarzbach M, Dimitrakopoulou-Strauss A. Dynamic (18)F-fluorodeoxyglucose positron emission tomography/CT in hibernoma: enhanced tracer uptake mimicking liposarcoma. World J Radiol. 2013;5(12):498–502. PubMed PMID: 24379937. Pubmed Central PMCID: 3874507.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Agrawal A, Kembhavi S, Purandare N, Shah S, Rangarajan V. Report of two cases of fluorodeoxyglucose positron emission tomography/computed tomography appearance of hibernoma: a rare benign tumor. Indian J Nucl Med. 2014;29(1):40–2. PubMed PMID: 24591783. Pubmed Central PMCID: 3928751.

    Article  PubMed Central  PubMed  Google Scholar 

  44. Zingaretti MC, Crosta F, Vitali A, Guerrieri M, Frontini A, Cannon B, et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. FASEB J. 2009;23(9):3113–20. PubMed PMID: 19417078.

    Article  CAS  PubMed  Google Scholar 

  45. Yoneshiro T, Ogawa T, Okamoto N, Matsushita M, Aita S, Kameya T, et al. Impact of UCP1 and beta3AR gene polymorphisms on age-related changes in brown adipose tissue and adiposity in humans. Int J Obes. 2013;37(7):993–8. PubMed PMID: 23032405.

    Article  CAS  Google Scholar 

  46. Smith RE, Hock RJ. Brown fat: thermogenic effector of arousal in hibernators. Science. 1963;140(3563):199–200. PubMed PMID: 13989560.

    Article  CAS  PubMed  Google Scholar 

  47. Buchsbaum M, Morrow L, Meyers D, Krentz A, Peterson G, Swan T, et al. Brown adipose tissue metabolic activity assessed with FDG-PET/CT correlates with BMI and glucose. Diabetologia. 2013;56.

    Google Scholar 

  48. Eycleshymer AC, S DM. A cross-section anatomy. New York: D. Appleton and Company; 1911.

    Google Scholar 

  49. Gray H. Anatomy of the human body. Philadelphia: Lea & Febiger; 1959.

    Google Scholar 

  50. Orava J, Nummenmaa L, Noponen T, Viljanen T, Parkkola R, Nuutila P, et al. Brown adipose tissue function is accompanied by cerebral activation in lean but not in obese humans. J Cereb Blood Flow Metab. 2014;34:1018–23. PubMed PMID: 24667912.

    Article  CAS  PubMed  Google Scholar 

  51. Volkow ND, Wang GJ, Telang F, Fowler JS, Goldstein RZ, Alia-Klein N, et al. Inverse association between BMI and prefrontal metabolic activity in healthy adults. Obesity. 2009;17(1):60–5. PubMed PMID: 18948965. Pubmed Central PMCID: 2681079.

    Article  PubMed Central  PubMed  Google Scholar 

  52. de Wit L, Luppino F, van Straten A, Penninx B, Zitman F, Cuijpers P. Depression and obesity: a meta-analysis of community-based studies. Psychiatry Res. 2010;178(2):230–5. PubMed PMID: 20462641.

    Article  PubMed  Google Scholar 

  53. Sarwer DB, Cohn NI, Gibbons LM, Magee L, Crerand CE, Raper SE, et al. Psychiatric diagnoses and psychiatric treatment among bariatric surgery candidates. Obes Surg. 2004;14(9):1148–56. PubMed PMID: 15527626. eng.

    Article  PubMed  Google Scholar 

  54. Rosenberger PHHK, Grilo CM. Psychiatric disorder comorbidity and association with eating disorders in bariatric surgery patients: a cross-sectional study using structured interview-based diagnosis. J Clin Psychiatry. 2006;67(7):6.

    Article  Google Scholar 

  55. Lier HO, Biringer E, Stubhaug B, Tangen T. Prevalence of psychiatric disorders before and 1 year after bariatric surgery: the role of shame in maintenance of psychiatric disorders in patients undergoing bariatric surgery. Nord J Psychiatry. 2013;67:89–96. PubMed PMID: 22587601. ENG.

    Article  PubMed  Google Scholar 

  56. Cunningham JL, Merrell CC, Sarr M, Somers KJ, McAlpine D, Reese M, et al. Investigation of antidepressant medication usage after bariatric surgery. Obes Surg. 2012;22(4):530–5. PubMed PMID: 21901283. eng.

    Article  PubMed  Google Scholar 

  57. Anderson JW, Greenway FL, Fujioka K, Gadde KM, McKenney J, O’Neil PM. Bupropion SR enhances weight loss: a 48-week double-blind, placebo- controlled trial. Obes Res. 2002;10(7):633–41. PubMed PMID: 12105285. eng.

    Article  CAS  PubMed  Google Scholar 

  58. Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry. 2010;71(10):1259–72. PubMed PMID: 21062615. eng.

    Article  PubMed  Google Scholar 

  59. Tolstoy L. Anna Karenina. Ebook: Gutenberg Project; 1998.

    Google Scholar 

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Acknowledgements

The authors thank Andrew Krentz, Linda Morrow, and Marcus Hompesch for their support and useful advice at varied stages of the preparation of this chapter. Gisela Peterson and Laurel Glockler provided careful data organization support. George Madirossian provided assistance with scanner calibration and phantoms, Tim Erickson with electronic records, and Steven Hardy with file organization and scanner operation. Didier Laurent made useful suggestions for the data analysis.

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Authors and Affiliations

  1. Department of Psychiatry and Radiology, University of California, San Diego, San Diego, CA, USA

    Monte S. Buchsbaum MD

  2. Department of Psychiatry, University of California, San Diego, San Diego, CA, USA

    Alex DeCastro MS

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  1. Monte S. Buchsbaum MD
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Correspondence to Monte S. Buchsbaum MD .

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Editors and Affiliations

  1. Profil Institute for Clinical Research, Chula Vista, California, USA

    Andrew J. Krentz

  2. Profil Institute for Clinical Research, Chula Vista, California, USA

    Lutz Heinemann

  3. Profil Institute for Clinical Research, Chula Vista, California, USA

    Marcus Hompesch

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Buchsbaum, M.S., DeCastro, A. (2015). Positron-Emission Tomography and Computed Tomography Measurement of Brown Fat Thermal Activation: Key Tools for Developing Novel Pharmacotherapeutics for Obesity and Diabetes. In: Krentz, A., Heinemann, L., Hompesch, M. (eds) Translational Research Methods for Diabetes, Obesity and Cardiometabolic Drug Development. Springer, London. https://doi.org/10.1007/978-1-4471-4920-0_5

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