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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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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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Affiliations

  1. Department of Cell and Molecular Biology, Karolinska Institute, SE-171 77 Stockholm, Sweden

    • Kirsty L. Spalding
    • , Erik Arner
    • , Olaf Bergmann
    •  & Jonas Frisén
  2. Institute for Theoretical Biology (ITB), Humboldt University Berlin and Charité, Invalidenstrasse 43, 10115 Berlin, Germany

    • Pål O. Westermark
  3. Institute of Applied and Computational Mathematics, Foundation of Research and Technology, 71110 Heraklion Crete, Greece

    • Samuel Bernard
  4. Center for Accelerator Mass Spectrometry, Lawrence Livermore National Laboratory, 7000 East Avenue, L-397, Livermore, California 94551, USA

    • Bruce A. Buchholz
  5. Department of Medicine, Karolinska University Hospital, SE-141 86 Stockholm, Sweden

    • Lennart Blomqvist
    • , Johan Hoffstedt
    • , Hernan Concha
    • , Moustapha Hassan
    • , Mikael Rydén
    •  & Peter Arner
  6. Division of Surgery, Department of Clinical Science, Danderyds Hospital, Karolinska Institutet, SE-182 88 Stockholm, Sweden

    • Erik Näslund
  7. Department of Mathematics, Stockholm University, 106 91 Stockholm, Sweden

    • Tom Britton

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

Supplementary information

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    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.

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https://doi.org/10.1038/nature06902

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