Remodeling of lipid droplets during lipolysis and growth in adipocytes

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2012
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Paar, Margret
Steiner, Noemi
Magnes, Christoph
Sinner, Frank
Kolb, Dagmar
Lass, Achim
Zimmermann, Robert
Kohlwein, Sepp
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Journal of Biological Chemistry ; 287 (2012), 14. - pp. 11164-11173. - ISSN 0021-9258. - eISSN 1083-351X
Abstract
Synthesis, storage, and turnover of triacylglycerols (TAGs) in adipocytes are critical cellular processes to maintain lipid and energy homeostasis in mammals. TAGs are stored in metabolically highly dynamic lipid droplets (LDs), which are believed to undergo fragmentation and fusion under lipolytic and lipogenic conditions, respectively. Time lapse fluorescence microscopy showed that stimulation of lipolysis in 3T3-L1 adipocytes causes progressive shrinkage and almost complete degradation of all cellular LDs but without any detectable fragmentation into micro-LDs (mLDs). However, mLDs were rapidly formed after induction of lipolysis in the absence of BSA in the culture medium that acts as a fatty acid scavenger. Moreover, mLD formation was blocked by the acyl-CoA synthetase inhibitor triacsin C, implicating that mLDs are synthesized de novo in response to cellular fatty acid overload. Using label-free coherent anti-Stokes Raman scattering microscopy, we demonstrate that LDs grow by transfer of lipids from one organelle to another. Notably, this lipid transfer between closely associated LDs is not a rapid and spontaneous process but rather occurs over several h and does not appear to require physical interaction over large LD surface areas. These data indicate that LD growth is a highly regulated process leading to the heterogeneous LD size distribution within and between individual cells. Our findings suggest that lipolysis and lipogenesis occur in parallel in a cell to prevent cellular fatty acid overflow. Furthermore, we propose that formation of large LDs requires a yet uncharacterized protein machinery mediating LD interaction and lipid transfer.
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ISO 690PAAR, Margret, Christian JÜNGST, Noemi STEINER, Christoph MAGNES, Frank SINNER, Dagmar KOLB, Achim LASS, Robert ZIMMERMANN, Andreas ZUMBUSCH, Sepp KOHLWEIN, Heimo WOLINSKI, 2012. Remodeling of lipid droplets during lipolysis and growth in adipocytes. In: Journal of Biological Chemistry. 287(14), pp. 11164-11173. ISSN 0021-9258. eISSN 1083-351X. Available under: doi: 10.1074/jbc.M111.316794
BibTex
@article{Paar2012-03-30Remod-21123,
  year={2012},
  doi={10.1074/jbc.M111.316794},
  title={Remodeling of lipid droplets during lipolysis and growth in adipocytes},
  number={14},
  volume={287},
  issn={0021-9258},
  journal={Journal of Biological Chemistry},
  pages={11164--11173},
  author={Paar, Margret and Jüngst, Christian and Steiner, Noemi and Magnes, Christoph and Sinner, Frank and Kolb, Dagmar and Lass, Achim and Zimmermann, Robert and Zumbusch, Andreas and Kohlwein, Sepp and Wolinski, Heimo}
}
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