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:

No evidence of white adipocyte browning after endurance exercise training in obese men

International Journal of Obesity volume 42, pages 721–727 (2018)Cite this article

Subjects

Abstract

Background/Objectives:

The phenomenon of adipocyte ‘beiging’ involves the conversion of non-classic brown adipocytes to brown-like adipose tissue with thermogenic, fat-burning properties, and this phenomenon has been shown in rodents to slow the progression of obesity-associated metabolic diseases. Rodent studies consistently report adipocyte beiging after endurance exercise training, indicating that increased thermogenic capacity in these adipocytes may underpin the improved health benefits of exercise training. The aim of this study was to determine whether prolonged endurance exercise training induces beige adipogenesis in subcutaneous adipose tissues of obese men.

Subjects/Methods:

Molecular markers of beiging were examined in adipocytes obtained from abdominal subcutaneous (AbSC) and gluteofemoral (GF) subcutaneous adipose tissues before and after 6 weeks of endurance exercise training in obese men (n=6, 37.3±2.3 years, 30.1±2.3 kg m–2).

Results:

The mRNAs encoding the brown or beige adipocyte-selective proteins were very lowly expressed in AbSC and GF adipose tissues and exercise training did not alter the mRNA expression of UCP1, CD137, CITED, TBX1, LHX8 and TCF21. Using immunohistochemistry, neither multilocular adipocytes, nor UCP1 or CD137-positive adipocytes were detected in any sample. MicroRNAs known to regulate brown and/or beige adipose development were highly expressed in white adipocytes but endurance exercise training did not impact their expression.

Conclusions:

The present study reaffirms emerging data in humans demonstrating no evidence of white adipose tissue beiging in response to exercise training, and supports a growing body of work demonstrating divergence of brown/beige adipose location, molecular characterization and physiological function between rodents and humans.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Crowe S, Wu LE, Economou C, Turpin SM, Matzaris M, Hoehn KL et al. Pigment epithelium-derived factor contributes to insulin resistance in obesity. Cell Metab 2009; 10: 40–47.

    Article  CAS  Google Scholar 

  2. Rosen ED, Spiegelman BM . What we talk about when we talk about fat. Cell 2014; 156: 20–44.

    Article  CAS  Google Scholar 

  3. Tsiloulis T, Watt MJ . Exercise and the regulation of adipose tissue metabolism. Prog Mol Biol Transl Sci 2015; 135: 175–201.

    Article  CAS  Google Scholar 

  4. Harms M, Seale P . Brown and beige fat: development, function and therapeutic potential. Nat Med 2013; 19: 1252–1263.

    Article  CAS  Google Scholar 

  5. Carey AL, Formosa MF, Van Every B, Bertovic D, Eikelis N, Lambert GW et al. Ephedrine activates brown adipose tissue in lean but not obese humans. Diabetologia 2013; 56: 147–155.

    Article  CAS  Google Scholar 

  6. 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 

  7. 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 

  8. Mulya A, Kirwan JP . Brown and beige adipose tissue: therapy for obesity and its comorbidities? Endocrinol Metab Clin North Am 2016; 45: 605–621.

    Article  Google Scholar 

  9. 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: 366–376.

    Article  CAS  Google Scholar 

  10. Petrovic N, Walden TB, Shabalina IG, Timmons JA, Cannon B, Nedergaard J . Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem 2010; 285: 7153–7164.

    Article  CAS  Google Scholar 

  11. Young P, Arch JR, Ashwell M . Brown adipose tissue in the parametrial fat pad of the mouse. FEBS Lett 1984; 167: 10–14.

    Article  CAS  Google Scholar 

  12. Bertholet AM, Kazak L, Chouchani ET, Bogaczynska MG, Paranjpe I, Wainwright GL et al. Mitochondrial patch clamp of beige adipocytes reveals UCP1-positive and UCP1-negative cells both exhibiting futile creatine cycling. Cell Metab 2017; 25: 811–822 e4.

    Article  CAS  Google Scholar 

  13. Shabalina IG, Petrovic N, de Jong JM, Kalinovich AV, Cannon B, Nedergaard J . UCP1 in brite/beige adipose tissue mitochondria is functionally thermogenic. Cell Rep 2013; 5: 1196–1203.

    Article  CAS  Google Scholar 

  14. Long JZ, Svensson KJ, Tsai L, Zeng X, Roh HC, Kong X et al. A smooth muscle-like origin for beige adipocytes. Cell Metab 2014; 19: 810–820.

    Article  CAS  Google Scholar 

  15. Rosenwald M, Wolfrum C . The origin and definition of brite versus white and classical brown adipocytes. Adipocyte 2014; 3: 4–9.

    Article  CAS  Google Scholar 

  16. Sharp LZ, Shinoda K, Ohno H, Scheel DW, Tomoda E, Ruiz L et al. Human BAT possesses molecular signatures that resemble beige/brite cells. PLoS One 2012; 7: e49452.

    Article  CAS  Google Scholar 

  17. Jespersen NZ, Larsen TJ, Peijs L, Daugaard S, Homoe P, Loft A et al. A classical brown adipose tissue mRNA signature partly overlaps with brite in the supraclavicular region of adult humans. Cell Metab 2013; 17: 798–805.

    Article  CAS  Google Scholar 

  18. Carey AL, Vorlander C, Reddy-Luthmoodoo M, Natoli AK, Formosa MF, Bertovic DA et al. Reduced UCP-1 content in in vitro differentiated beige/brite adipocytes derived from preadipocytes of human subcutaneous white adipose tissues in obesity. PLoS ONE 2014; 9: e91997.

    Article  Google Scholar 

  19. Stanford KI, Middelbeek RJ, Goodyear LJ . Exercise effects on white adipose tissue: beiging and metabolic adaptations. Diabetes 2015; 64: 2361–2368.

    Article  CAS  Google Scholar 

  20. Knudsen JG, Murholm M, Carey AL, Bienso RS, Basse AL, Allen TL et al. Role of IL-6 in exercise training- and cold-induced UCP1 expression in subcutaneous white adipose tissue. PLoS One 2014; 9: e84910.

    Article  Google Scholar 

  21. 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: 463–468.

    Article  Google Scholar 

  22. Roberts LD, Bostrom P, O'Sullivan JF, Schinzel RT, Lewis GD, Dejam A et al. Beta-aminoisobutyric acid induces browning of white fat and hepatic beta-oxidation and is inversely correlated with cardiometabolic risk factors. Cell Metab 2014; 19: 96–108.

    Article  CAS  Google Scholar 

  23. Rao RR, Long JZ, White JP, Svensson KJ, Lou J, Lokurkar I et al. Meteorin-like is a hormone that regulates immune-adipose interactions to increase beige fat thermogenesis. Cell 2014; 157: 1279–1291.

    Article  CAS  Google Scholar 

  24. Kjaer M, Christensen NJ, Sonne B, Richter EA, Galbo H . Effect of exercise on epinephrine turnover in trained and untrained male subjects. J Appl Physiol (1985) 1985; 59: 1061–1067.

    Article  CAS  Google Scholar 

  25. Sidossis LS, Porter C, Saraf MK, Borsheim E, Radhakrishnan RS, Chao T et al. Browning of subcutaneous white adipose tissue in humans after severe adrenergic stress. Cell Metab 2015; 22: 219–227.

    Article  CAS  Google Scholar 

  26. Nakhuda A, Josse AR, Gburcik V, Crossland H, Raymond F, Metairon S et al. Biomarkers of browning of white adipose tissue and their regulation during exercise- and diet-induced weight loss. Am J Clin Nutr 2016; 104: 557–565.

    Article  CAS  Google Scholar 

  27. Norheim F, Langleite TM, Hjorth M, Holen T, Kielland A, Stadheim HK et al. The effects of acute and chronic exercise on PGC-1α, irisin and browning of subcutaneous adipose tissue in humans. FEBS J 2014; 281: 739–749.

    Article  CAS  Google Scholar 

  28. Pino MF, Parsons SA, Smith SR, Sparks LM . Active individuals have high mitochondrial content and oxidative markers in their abdominal subcutaneous adipose tissue. Obesity (Silver Spring, MD) 2016; 24: 2467–2470.

    Article  CAS  Google Scholar 

  29. Camera DM, Anderson MJ, Hawley JA, Carey AL . Short-term endurance training does not alter the oxidative capacity of human subcutaneous adipose tissue. Eur J Appl Physiol 2010; 109: 307–316.

    Article  Google Scholar 

  30. Tsiloulis T, Pike J, Powell D, Rossello FJ, Canny BJ, Meex RC et al. Impact of endurance exercise training on adipocyte microRNA expression in overweight men. FASEB J 2017; 31: 161–171.

    Article  CAS  Google Scholar 

  31. Lee P, Zhao JT, Swarbrick MM, Gracie G, Bova R, Greenfield JR et al. High prevalence of brown adipose tissue in adult humans. J Clin Endocrinol Metab 2011; 96: 2450–2455.

    Article  CAS  Google Scholar 

  32. Friedlander MR, Mackowiak SD, Li N, Chen W, Rajewsky N . miRDeep2 accurately identifies known and hundreds of novel microRNA genes in seven animal clades. Nucleic Acids Res 2012; 40: 37–52.

    Article  Google Scholar 

  33. Ritchie ME, Phipson B, Wu D, Hu Y, Law CW, Shi W et al. Limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res 2015; 43: e47.

    Article  Google Scholar 

  34. Wickham H . ggplot2: Elegant Graphics for Data Analysis. Springer-Verlag: New York, 2009.

    Book  Google Scholar 

  35. Law CW, Chen Y, Shi W, Smyth GK . Voom: precision weights unlock linear model analysis tools for RNA-seq read counts. Genome Biol 2014; 15: R29.

    Article  Google Scholar 

  36. Chen Y, Pan R, Pfeifer A . Regulation of brown and beige fat by microRNAs. Pharmacol Ther 2017; 170: 1–7.

    Article  CAS  Google Scholar 

  37. Ringholm S, Grunnet Knudsen J, Leick L, Lundgaard A, Munk Nielsen M, Pilegaard H . PGC-1alpha is required for exercise- and exercise training-induced UCP1 up-regulation in mouse white adipose tissue. PLoS ONE 2013; 8: e64123.

    Article  Google Scholar 

  38. Shen Y, Zhou H, Jin W, Lee HJ . Acute exercise regulates adipogenic gene expression in white adipose tissue. Biol Sport 2016; 33: 381–391.

    Article  CAS  Google Scholar 

  39. Xu X, Ying Z, Cai M, Xu Z, Li Y, Jiang SY et al. Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue. Am J Physiol Regul Integr Comp Physiol 2011; 300: R1115–R1125.

    Article  CAS  Google Scholar 

  40. Rönn T, Volkov P, Tornberg Å, Elgzyri T, Hansson O, Eriksson KF et al. Extensive changes in the transcriptional profile of human adipose tissue including genes involved in oxidative phosphorylation after a 6-month exercise intervention. Acta Physiologica 2014; 211: 188–200.

    Article  Google Scholar 

  41. Hilton C, Neville MJ, Karpe F . MicroRNAs in adipose tissue: their role in adipogenesis and obesity. Int J Obes (2005) 2013; 37: 325–332.

    Article  CAS  Google Scholar 

  42. Arner P, Kulyte A . MicroRNA regulatory networks in human adipose tissue and obesity. Nat Rev Endocrinol 2015; 11: 276–288.

    Article  CAS  Google Scholar 

  43. Price NL, Fernandez-Hernando C . miRNA regulation of white and brown adipose tissue differentiation and function. Biochim Biophys Acta 2016; 1861: 2104–2110.

    Article  CAS  Google Scholar 

  44. Loh RKC, Kingwell BA, Carey AL . Human brown adipose tissue as a target for obesity management; beyond cold-induced thermogenesis. Obes Rev 2017; 18: 1227–1242.

    Article  CAS  Google Scholar 

  45. Stanford KI, Goodyear LJ . Exercise regulation of adipose tissue. Adipocyte 2016; 5: 153–162.

    Article  CAS  Google Scholar 

  46. Oldfield BJ, McLachlan EM . An analysis of the sympathetic preganglionic neurons projecting from the upper thoracic spinal roots of the cat. J Comp Neurol 1981; 196: 329–345.

    Article  CAS  Google Scholar 

  47. Scheele C . Adipose adaptation to exercise training –increased metabolic rate but no signs of browning. Acta Physiologica 2014; 211: 11–12.

    Article  CAS  Google Scholar 

  48. Kjaer M, Farrell PA, Christensen NJ, Galbo H . Increased epinephrine response and inaccurate glucoregulation in exercising athletes. J Appl Physiol (1985) 1986; 61: 1693–1700.

    Article  CAS  Google Scholar 

  49. Helge JW, Stallknecht B, Pedersen BK, Galbo H, Kiens B, Richter EA . The effect of graded exercise on IL-6 release and glucose uptake in human skeletal muscle. J Physiol 2003; 546: 299–305.

    Article  CAS  Google Scholar 

  50. Xue R, Lynes MD, Dreyfuss JM, Shamsi F, Schulz TJ, Zhang H et al. Clonal analyses and gene profiling identify genetic biomarkers of the thermogenic potential of human brown and white preadipocytes. Nat Med 2015; 21: 760–768.

    Article  CAS  Google Scholar 

  51. Boquest AC, Shahdadfar A, Fronsdal K, Sigurjonsson O, Tunheim SH, Collas P et al. Isolation and transcription profiling of purified uncultured human stromal stem cells: alteration of gene expression after in vitro cell culture. Mol Biol Cell 2005; 16: 1131–1141.

    Article  CAS  Google Scholar 

  52. Zuriaga MA, Fuster JJ, Gokce N, Walsh K . Humans and mice display opposing patterns of “browning” gene expression in visceral and subcutaneous white adipose tissue depots. Front Cardiovasc Med 2017; 4: 27.

    Article  Google Scholar 

  53. Vosselman MJ, Hoeks J, Brans B, Pallubinsky H, Nascimento EB, van der Lans AA et al. Low brown adipose tissue activity in endurance-trained compared with lean sedentary men. Int J Obesity (2005) 2015; 39: 1696–1702.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Professor Ken Ho (University of Queensland) for the brown adipose tissue sample. This work was supported by the National Health and Medical Research Council of Australia (NHMRC, APP1098972) and MJW is supported by a Senior Research Fellowship from the NHMRC (APP1077703).

Author information

Authors and Affiliations

  1. and the Department of Physiology, Monash Biomedicine Discovery Institute, Metabolic Disease and Obesity Program, Monash University, Clayton, Victoria, Australia

    T Tsiloulis, J Bayliss, B Canny, R C R Meex & M J Watt

  2. Metabolic and Vascular Physiology Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, Australia

    A L Carey

  3. School of Medicine, Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia

    B Canny

  4. Department of Human Biology, School of Nutrition and Translational Research in Metabolism (NUTRIM), Maastricht University, Maastricht, The Netherlands

    R C R Meex

Authors
  1. T Tsiloulis
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A L Carey
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Bayliss
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B Canny
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R C R Meex
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M J Watt
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M J Watt.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tsiloulis, T., Carey, A., Bayliss, J. et al. No evidence of white adipocyte browning after endurance exercise training in obese men. Int J Obes 42, 721–727 (2018). https://doi.org/10.1038/ijo.2017.295

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2017.295

This article is cited by

Search

Advanced search

Quick links