Dynamics of human adipose lipid turnover in health and metabolic disease


Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes1. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, here we determined lipid age by measuring 14C derived from above ground nuclear bomb tests in adipocyte lipids. We report that during the average ten-year lifespan of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult ages and does not differ between genders. Adipocyte lipid turnover, however, is strongly related to conditions with disturbed lipid metabolism. In obesity, triglyceride removal rate (lipolysis followed by oxidation) is decreased and the amount of triglycerides stored each year is increased. In contrast, both lipid removal and storage rates are decreased in non-obese patients diagnosed with the most common hereditary form of dyslipidaemia, familial combined hyperlipidaemia. Lipid removal rate is positively correlated with the capacity of adipocytes to break down triglycerides, as assessed through lipolysis, and is inversely related to insulin resistance. Our data support a mechanism in which adipocyte lipid storage and removal have different roles in health and pathology. High storage but low triglyceride removal promotes fat tissue accumulation and obesity. Reduction of both triglyceride storage and removal decreases lipid shunting through adipose tissue and thus promotes dyslipidaemia. We identify adipocyte lipid turnover as a novel target for prevention and treatment of metabolic disease.

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Figure 1: Atmospheric 14 C over time and its use to determine lipid age and adipocyte age.
Figure 2: Relationship between adipocyte size and lipid age.
Figure 3: Lipid turnover in subcutaneous fat.
Figure 4: Correlation between lipid turnover and adipocyte lipolysis.


  1. 1

    Klein, R. A., Halliday, D. & Pittet, P. G. The use of 13-methyltetradecanoic acid as an indicator of adipose tissue turnover. Lipids 15, 572–579 (1980)

    CAS  Article  Google Scholar 

  2. 2

    Mårin, P., Oden, B. & Björntorp, P. Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. J. Clin. Endocrinol. Metab. 80, 239–243 (1995)

    PubMed  Google Scholar 

  3. 3

    Mårin, P., Rebuffe-Scrive, M. & Björntorp, P. Uptake of triglyceride fatty acids in adipose tissue in vivo in man. Eur. J. Clin. Invest. 20, 158–165 (1990)

    Article  Google Scholar 

  4. 4

    Strawford, A., Antelo, F., Christiansen, M. & Hellerstein, M. K. Adipose tissue triglyceride turnover, de novo lipogenesis, and cell proliferation in humans measured with 2H2O. Am. J. Physiol. 286, E577–E588 (2004)

    CAS  Google Scholar 

  5. 5

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

    CAS  Article  ADS  Google Scholar 

  6. 6

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

    CAS  Article  Google Scholar 

  7. 7

    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)

    CAS  Article  Google Scholar 

  8. 8

    Perl, S. et al. Significant human β-cell turnover is limited to the first three decades of life as determined by in vivo thymidine analog incorporation and radiocarbon dating. J. Clin. Endocrinol. Metab. 95, E234–E239 (2010)

    CAS  Article  Google Scholar 

  9. 9

    Spalding, K. L. et al. Dynamics of fat cell turnover in humans. Nature 453, 783–787 (2008)

    CAS  Article  ADS  Google Scholar 

  10. 10

    Bergmann, O. et al. Evidence for cardiomyocyte renewal in humans. Science 324, 98–102 (2009)

    CAS  Article  ADS  Google Scholar 

  11. 11

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

    CAS  Article  ADS  Google Scholar 

  12. 12

    Bernard, S., Frisen, J. & Spalding, K. L. A mathematical model for the interpretation of nuclear bomb test derived 14C incorporation in biological systems. Nucl. Instrum. Meth. B 268, 1295–1298 (2010)

    CAS  Article  ADS  Google Scholar 

  13. 13

    Ekstedt, B. & Olivecrona, T. Uptake and release of fatty acids by rat adipose tissue: last in to first out? Lipids 5, 858–860 (1970)

    CAS  Article  Google Scholar 

  14. 14

    Kerpel, S., Shafrir, E. & Shapiro, B. Mechanism of fatty acid assimilation in adipose tissue. Biochim. Biophys. Acta 46, 495–504 (1961)

    CAS  Article  Google Scholar 

  15. 15

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

    Article  Google Scholar 

  16. 16

    Grundy, S. M. Chait, A & Brunzell, J. D. Familial combined hyperlipidemia workshop. Arterioscler. Thromb. Vasc. Biol. 7, 203–207 (1987)

    Google Scholar 

  17. 17

    Langin, D. et al. Adipocyte lipases and defect of lipolysis in human obesity. Diabetes 54, 3190–3197 (2005)

    CAS  Article  Google Scholar 

  18. 18

    Reynisdottir, S., Eriksson, M., Angelin, B. & Arner, P. Impaired activation of adipocyte lipolysis in familial combined hyperlipidemia. J. Clin. Invest. 95, 2161–2169 (1995)

    CAS  Article  Google Scholar 

  19. 19

    van der Kallen, C. J. et al. Evidence of insulin resistant lipid metabolism in adipose tissue in familial combined hyperlipidemia, but not type 2 diabetes mellitus. Atherosclerosis 164, 337–346 (2002)

    CAS  Article  Google Scholar 

  20. 20

    Ayyobi, A. F. & Brunzell, J. D. Lipoprotein distribution in the metabolic syndrome, type 2 diabetes mellitus, and familial combined hyperlipidemia. Am. J. Cardiol. 92, 27–33 (2003)

    Article  Google Scholar 

  21. 21

    Arner, P. Is familial combined hyperlipidaemia a genetic disorder of adipose tissue? Curr. Opin. Lipidol. 8, 89–94 (1997)

    CAS  Article  Google Scholar 

  22. 22

    de Graaf, J., Veerkamp, M. J. & Stalenhoef, A. F. Metabolic pathogenesis of familial combined hyperlipidaemia with emphasis on insulin resistance, adipose tissue metabolism and free fatty acids. J. R. Soc. Med. 95 (suppl. 42). 46–53 (2002)

    CAS  Article  Google Scholar 

  23. 23

    Blaak, E. E. et al. Fat oxidation before and after a high fat load in the obese insulin-resistant state. J. Clin. Endocrinol. Metab. 91, 1462–1469 (2006)

    CAS  Article  ADS  Google Scholar 

  24. 24

    Houmard, J. A. Intramuscular lipid oxidation and obesity. Am. J. Physiol. Regul. Integr. Comp. Physiol. 294, R1111–R1116 (2008)

    CAS  Article  Google Scholar 

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This study was supported by the Swedish Research Council, Swedish Foundation for Strategic Research, Swedish Heart and Lung Foundation, Novo Nordic Foundation, Swedish Diabetes Foundation, Strategic Research Program in Diabetes at the Karolinska Institutet, Swedish Cancer Society, Uppsala BIO, Sweden, NIH/NCRR Grant RR13461, ERC grant 261258-HUFATREG and by the projects ‘Hepatic and adipose tissue and functions in the metabolic syndrome’ (HEPADIP, http://www.hepadip.org/) and ‘Adipokines as drug targets to combat adverse effects of excess adipose tissue’ (ADAPT, http://www.adapt-eu.net), which were supported by the European Commission as an Integrated Project under the 6th and the 7th Framework Programmes (contract LSHM-CT-2005-018734 and contract HEALTH-F2-2008-201100). This work was performed in part under the auspices of the US Department of Energy by Lawrence Livermore National Laboratory under contract DE-AC52-07NA27344. The authors would like to acknowledge E. Sjölin, K. Wåhlén, B.-M. Leijonhufvud, K. Hertel and Y. Widlund for technical assistance. We would like to thank F. Barnabé-Heider and J. Frisén for useful comments on the manuscript.

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K.L.S. and P.A. designed the study and wrote the manuscript together with K.N.F. and S.B. M.R. co-ordinated writing and data assembly. S.B. and E.A. were responsible for the modelling. K.L.S. performed sample preparation. M.S., G.P., B.A.B., P.S. and J.L. performed 14C accelerator mass spectrometry measurements. P.A., M.E., T.S. and H.H. collected clinical material.

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Correspondence to Peter Arner or Kirsty L. Spalding.

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The authors declare no competing financial interests.

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Arner, P., Bernard, S., Salehpour, M. et al. Dynamics of human adipose lipid turnover in health and metabolic disease. Nature 478, 110–113 (2011). https://doi.org/10.1038/nature10426

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