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Dynamics of human adipose lipid turnover in health and metabolic disease

Abstract

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.

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Acknowledgements

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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Contributions

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.

Corresponding authors

Correspondence to Peter Arner or Kirsty L. Spalding.

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The authors declare no competing financial interests.

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The file contains Supplementary Text and Data, Supplementary Figures 1-3 with legends and additional references. (PDF 428 kb)

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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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