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Dynamics of fat cell turnover in humans


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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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).

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