Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Clinical Studies and Practice

Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans

Abstract

Background:

Brown adipose tissue (BAT) is involved in the regulation of whole-body energy expenditure and adiposity. Some clinical studies have reported an association between BAT and blood glucose in humans.

Objective:

To examine the impact of BAT on glucose metabolism, independent of that of body fatness, age and sex in healthy adult humans.

Methods:

Two hundred and sixty healthy volunteers (184 males and 76 females, 20–72 years old) underwent fluorodeoxyglucose-positron emission tomography and computed tomography after 2 h of cold exposure to assess maximal BAT activity. Blood parameters including glucose, HbA1c and low-density lipoprotein (LDL)/high-density lipoprotein-cholesterol were measured by conventional methods, and body fatness was estimated from body mass index (BMI), body fat mass and abdominal fat area. The impact of BAT on body fatness and blood parameters was determined by logistic regression with the use of univariate and multivariate models.

Results:

Cold-activated BAT was detected in 125 (48%) out of 260 subjects. When compared with subjects without detectable BAT, those with detectable BAT were younger and showed lower adiposity-related parameters such as the BMI, body fat mass and abdominal fat area. Although blood parameters were within the normal range in the two subject groups, HbA1c, total cholesterol and LDL-cholesterol were significantly lower in the BAT-positive group. Blood glucose also tended to be lower in the BAT-positive group. Logistic regression demonstrated that BAT, in addition to age and sex, was independently associated with BMI, body fat mass, and abdominal visceral and subcutaneous fat areas. For blood parameters, multivariate analysis after adjustment for age, sex and body fatness revealed that BAT was a significantly independent determinant of glucose and HbA1c.

Conclusion:

BAT, independent of age, sex and body fatness, has a significant impact on glucose metabolism in adult healthy humans.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  1. 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: 1500–1508.

    Article  CAS  Google Scholar 

  2. 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: 1509–1517.

    Article  CAS  Google Scholar 

  3. 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: 1518–1525.

    Article  CAS  Google Scholar 

  4. 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: 1526–1531.

    Article  CAS  Google Scholar 

  5. 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: 13–16.

    Article  Google Scholar 

  6. 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: 272–279.

    Article  CAS  Google Scholar 

  7. Yoneshiro T, Aita S, Matsushita M, Kayahara T, Kameya T, Kawai Y et al. Recruited brown adipose tissue as an anti-obesity agent in humans. J Clin Invest 2013; 123: 3404–3408.

    Article  CAS  Google Scholar 

  8. 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 (Silver Spring) 2011; 19: 1755–1760.

    Article  Google Scholar 

  9. Lee P, Swarbrick MM . Ho KKY. Brown adipose tissue in adult humans. A metabolic renaissance. Endocr Rev 2013; 34: 413–438.

    Article  CAS  Google Scholar 

  10. Vosselman MJ, van Marken Lichtenbelt WD, Schrauwen P . Energy dissipation in brown adipose tissue: From mice to men. Mol Cell Endocrinol 2013; 379: 43–50.

    Article  CAS  Google Scholar 

  11. Zafrir B . Brown adipose tissue: research milestones of a potential player in human energy balance and obesity. Horm Metab Res 2013; 45: 774–785.

    Article  CAS  Google Scholar 

  12. Au-Yong IT, Thorn N, Ganatra R, Perkins AC, Symonds ME . Brown adipose tissue and seasonal variation in humans. Diabetes 2009; 58: 2583–2587.

    Article  CAS  Google Scholar 

  13. 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: 1789–1793.

    Article  CAS  Google Scholar 

  14. Lee P, Greenfield JR, Ho KK, Fulham MJ . A critical appraisal of the prevalence and metabolic significance of brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab 2010; 299: E601–E606.

    Article  CAS  Google Scholar 

  15. 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: 192–199.

    Article  CAS  Google Scholar 

  16. 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: 836–842.

    Article  Google Scholar 

  17. Persichetti A, Scluto R, Rea S, Basciani S, Lubrano C, Mariani S et al. Prevalence, mass, and glucose-uptake activity of 18F-FDG-detected brown adipose in humans living in a temperate zone of Italy. PLoS One 2013; 8: e63391.

    Article  CAS  Google Scholar 

  18. Nishio M, Yoneshiro T, Nakahara M, Suzuki S, Saeki K, Hasegawa M et al. Production of functional classical brown adipocytes from human pluripotent stem cells using specific hemopoietin cocktail without gene transfer. Cell Metab 2012; 16: 394–406.

    Article  CAS  Google Scholar 

  19. Stanford KI, Middelbeek RJW, Townsend KL, An D, Nygaard EB, Hitchcox KM et al. Brown adipose tissue regulates glucose homeostasis and insulin sensitivity. J Clin Invest 2013; 123: 215–223.

    Article  CAS  Google Scholar 

  20. Vallerand AL, Pesusse F, Bukowiecki LJ . Cold exposure potentiates the effect of insulin on in vivo glucose uptake. Am J Physiol 1987; 253: E179–R186.

    CAS  Google Scholar 

  21. Shimizu Y, Nikami H, Saito M . Sympathetic activation of glucose utilization in brown adipose tissue in rats. J Biochem 1991; 110: 688–692.

    Article  CAS  Google Scholar 

  22. Gasparetti AL, de Souza CT, Pereira-da-Silva M, Oliveira RLGS, Saad MJA, Carneiro EM et al. Cold exposure induces tissue-specific modulation of the insulin-signalling pathway in Rattus norvegicus. J Physiol 2003; 552: 149–162.

    Article  CAS  Google Scholar 

  23. Chondronikola M, Hurren NM, Porter G, Annamalai P, Elena Volpi E, Borsheim E et al. Effect of prolonged, mild cold exposure on metabolic regulation in insulin resistant overweight and obese men. FASEB J 2013; 27, Meeting Abstract Supplement 1154.20.

    Google Scholar 

  24. Shimizu Y, Kielar D, Minokoshi Y, Shimazu T . Noradrenaline increases glucose transport into brown adipocytes in culture by a mechanism different from that of insulin. Biochem J 1996; 314: 485–490.

    Article  CAS  Google Scholar 

  25. Villarroya J, Cereijo R, Villarroya F . An endocrine role for brown adipose tissue? Am J Physiol Endocrinol Metab 2013; 305: E567–E572.

    Article  CAS  Google Scholar 

  26. Lee P, Werner CD, Kebebew E, Celi FS . Functional thermogenic beige adipogenesis is inducible in human neck fat. Int J Obes (Lond) 2014; 38: 170–176.

    Article  Google Scholar 

  27. Lee P, Brychta RJ, Linderman J, Smith S, Chen KY, Celi FS . Mild cold exposure modulates fibroblast growth factor 21 (FGF21) diurnal rhythm in humans: relationship between FGF21 levels, lipolysis, and cold-induced thermogenesis. J Clin Endocrinol Metab 2013; 98: E98–E102.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This study was supported by a Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (22590227), and a Special Research Grant from Tenshi College.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Saito.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Matsushita, M., Yoneshiro, T., Aita, S. et al. Impact of brown adipose tissue on body fatness and glucose metabolism in healthy humans. Int J Obes 38, 812–817 (2014). https://doi.org/10.1038/ijo.2013.206

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2013.206

Keywords

This article is cited by

Search

Quick links