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Dynamics of fat cell turnover in humans

Abstract

Obesity is increasing in an epidemic manner in most countries and constitutes a public health problem by enhancing the risk for cardiovascular disease and metabolic disorders such as type 2 diabetes1,2. Owing to the increase in obesity, life expectancy may start to decrease in developed countries for the first time in recent history3. The factors determining fat mass in adult humans are not fully understood, but increased lipid storage in already developed fat cells (adipocytes) is thought to be most important4,5. Here we show that adipocyte number is a major determinant for the fat mass in adults. However, the number of fat cells stays constant in adulthood in lean and obese individuals, even after marked weight loss, indicating that the number of adipocytes is set during childhood and adolescence. To establish the dynamics within the stable population of adipocytes in adults, we have measured adipocyte turnover by analysing the integration of 14C derived from nuclear bomb tests in genomic DNA6. Approximately 10% of fat cells are renewed annually at all adult ages and levels of body mass index. Neither adipocyte death nor generation rate is altered in early onset obesity, suggesting a tight regulation of fat cell number in this condition during adulthood. The high turnover of adipocytes establishes a new therapeutic target for pharmacological intervention in obesity.

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Figure 1: Fat mass is determined by both adipocyte number and size.
Figure 2: Adipocyte number remains stable in adulthood, although significant weight loss can result in a decrease in adipocyte volume.
Figure 3: Turnover of adipocytes in adulthood.
Figure 4: Effect of obesity on adipocyte generation and death.

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References

  1. Van Gaal, L. F., Mertens, I. L. & De Block, C. E. Mechanisms linking obesity with cardiovascular disease. Nature 444, 875–880 (2006)

    Article  ADS  CAS  Google Scholar 

  2. Kahn, S. E., Hull, R. L. & Utzschneider, K. M. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 444, 840–846 (2006)

    Article  ADS  CAS  Google Scholar 

  3. Olshansky, S. J. et al. A potential decline in life expectancy in the United States in the 21st century. N. Engl. J. Med. 352, 1138–1145 (2005)

    Article  CAS  Google Scholar 

  4. Bjorntorp, P. Effects of age, sex, and clinical conditions on adipose tissue cellularity in man. Metabolism 23, 1091–1102 (1974)

    Article  CAS  Google Scholar 

  5. Hirsch, J. & Batchelor, B. Adipose tissue cellularity in human obesity. Clin. Endocrinol. Metab. 5, 299–311 (1976)

    Article  CAS  Google Scholar 

  6. Spalding, K. L., Bhardwaj, R. D., Buchholz, B. A., Druid, H. & Frisen, J. Retrospective birth dating of cells in humans. Cell 122, 133–143 (2005)

    Article  CAS  Google Scholar 

  7. Prins, J. B. & O’Rahilly, S. Regulation of adipose cell number in man. Clin. Sci. (Lond.) 92, 3–11 (1997)

    Article  CAS  Google Scholar 

  8. Knittle, J. L., Timmers, K., Ginsberg-Fellner, F., Brown, R. E. & Katz, D. P. The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size. J. Clin. Invest. 63, 239–246 (1979)

    Article  CAS  Google Scholar 

  9. Miller, M. et al. Demonstration of de novo production of adipocytes in adult rats by biochemical and radioautographic techniques. J. Lipid Res. 25, 336–347 (1984)

    CAS  PubMed  Google Scholar 

  10. Kral, J. et al. Body composition and adipose tissue cellularity before and after jejuno-ileostomy in severely obese subjects. Eur. J. Clin. Inv. 7, 413–419 (1977)

    Article  CAS  Google Scholar 

  11. Björntorp, P. et al. Effect of an energy reduced dietry regimen in relation to adipose tissue cellularity in obese women. Am. J. Clin. Nut. 28, 445–452 (1975)

    Article  Google Scholar 

  12. Häger, A. et al. Adipose tissue cellularity in obese school girls before and after dietary intervention. Am. J. Clin. Nut. 31, 68–75 (1978)

    Article  Google Scholar 

  13. Sims, E. A. et al. Experimental obesity in man. Trans. Assoc. Am. Physicians 81, 153–170 (1968)

    CAS  PubMed  Google Scholar 

  14. Rodriguez, A. M., Elabd, C., Amri, E. Z., Ailhaud, G. & Dani, C. The human adipose tissue is a source of multipotent stem cells. Biochimie 87, 125–128 (2005)

    Article  CAS  Google Scholar 

  15. Petruschke, T. & Hauner, H. Tumor necrosis factor-α prevents the differentiation of human adipocyte precursor cells and causes delipidation of newly developed fat cells. J. Clin. Endocrinol. Metab. 76, 742–747 (1993)

    CAS  PubMed  Google Scholar 

  16. Prins, J. B., Walker, N. I., Winterford, C. M. & Cameron, D. P. Apoptosis of human adipocytes in vitro . Biochem. Biophys. Res. Commun. 201, 500–507 (1994)

    Article  CAS  Google Scholar 

  17. Cinti, S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J. Lipid Res. 46, 2347–2355 (2005)

    Article  CAS  Google Scholar 

  18. Bhardwaj, R. D. et al. Neocortical neurogenesis in humans is restricted to development. Proc. Natl Acad. Sci. USA 103, 12564–12568 (2006)

    Article  ADS  CAS  Google Scholar 

  19. De Vries, H. Atomic bomb effect: variation of radiocarbon in plants, shells, and snails in the past 4 years. Science 128, 250–251 (1958)

    Article  ADS  CAS  Google Scholar 

  20. Nydal, R. & Lovseth, K. Distribution of radiocarbon from nuclear tests. Nature 206, 1029–1031 (1965)

    Article  ADS  CAS  Google Scholar 

  21. Levin, I. & Kromer, B. The tropospheric 14CO2 level in mid latitudes of the northern hemisphere (1959–2003). Radiocarbon 46, 1261–1272 (2004)

    Article  CAS  Google Scholar 

  22. Spalding, K. L., Buchholz, B. A., Bergman, L. E., Druid, H. & Frisen, J. Forensics: age written in teeth by nuclear tests. Nature 437, 333–334 (2005)

    Article  ADS  CAS  Google Scholar 

  23. Libby, W. F., Berger, R., Mead, J. F., Alexander, G. V. & Ross, J. F. Replacement rates for human tissue from atmospheric radiocarbon. Science 146, 1170–1172 (1964)

    Article  ADS  CAS  Google Scholar 

  24. Harkness, D. D. Further investigations of the transfer of bomb 14C to man. Nature 240, 302–303 (1972)

    Article  ADS  CAS  Google Scholar 

  25. Altman, D. G. Practical Statistics for Medical Research pp 164 (Chapman & Hall, CRC, London, 1991)

    Google Scholar 

  26. Löfgren, P. et al. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the post-obese state. J. Clin. Endocrinol. Metab. 90, 6207–6213 (2005)

    Article  Google Scholar 

  27. Freedman D. S. et al. Relationship of childhood overweight to coronary heart disease. Risk factors in adulthood: The Bogalusa Heart Study. Pediatrics 108, 712–718 (2001)

    Article  Google Scholar 

  28. Raff, M. C. Size control: the regulation of cell numbers in animal development. Cell 26, 173–175 (1996)

    Article  Google Scholar 

  29. Joulia-Ekaza, D. & Cabello, G. Myostatin regulation of muscle development: molecular basis, natural mutations, physiopathological aspects. Exp. Cell Res. 312, 2401–2414 (2006)

    Article  Google Scholar 

  30. Stuiver, M. & Polach, H. A. Reporting on 14C data. Radiocarbon 19, 355–363 (1977)

    Article  Google Scholar 

Download references

Acknowledgements

We thank M. Stahlberg and T. Bergman for help with high-performance liquid chromatography (HPLC), D. Kurdyla, P. Zermeno and A. Williams for producing graphite, and S. Zdunek for comments on the statistics and modelling. This study was supported by grants from Knut och Alice Wallenbergs Stiftelse, the Human Frontiers Science Program, the Swedish Research Council, the Swedish Cancer Society, the Swedish Heart and Lung foundation, the Novo Nordic Foundation, the Swedish Diabetes Foundation, the Foundation for Strategic Research, the Karolinska Institute, the Tobias Foundation, AFA Life Insurance Health Foundation and NIH/NCRR (RR13461). This work was performed in part under the auspices of the US Department of Energy by University of California, Lawrence Livermore National Laboratory under contract W-7405-Eng-48.

Author Contributions K.L.S., P.A. and J.F. designed the study and wrote the manuscript. E.A., P.O.W., S.B., O.B. and T.B. were responsible for the modelling and statistics. K.L.S. and B.A.B. performed sample preparation and 14C accelerator mass spectrometry measurements. L.B., J.H. and E.N. collected clinical material. H.C., M.H. and M.R. performed studies on fat cell purity.

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Correspondence to Kirsty L. Spalding, Jonas Frisén or Peter Arner.

Supplementary information

Supplementary information

The file contains Supplementary Notes including model and curve fit for fat cell data measuring average fat cell volume against body fat mass; Supplementary Table showing all data from the thirty-five people whose adipose DNA was carbon dated; modelling of 14C data; methodologies and additional references. (PDF 1007 kb)

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Spalding, K., Arner, E., Westermark, P. et al. Dynamics of fat cell turnover in humans. Nature 453, 783–787 (2008). https://doi.org/10.1038/nature06902

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