Journal of Biological Chemistry
Volume 287, Issue 14, 30 March 2012, Pages 11164-11173
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Cell Biology
Remodeling of Lipid Droplets during Lipolysis and Growth in Adipocytes*

https://doi.org/10.1074/jbc.M111.316794Get rights and content
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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.

Adipocyte
Lipid Droplets
Lipid Metabolism
Lipogenesis
Lipolysis
Lipotoxicity
CARS
Fragmentation
Fusion
Time Lapse Imaging

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*

This work was supported in part by grants from the Austrian Science Funds, FWF, Project LIPOTOX F3005-B12 (to S. D. K.) and Ph.D. Program Molecular Enzymology, Project W901-B05, and the Austrian Federal Government for Science and Research (Project GOLD, in the framework of the Austrian Genome Program GEN-AU) (to S. D. K. and H. W.).

This article contains supplemental Movies S1–S4.

1

Both authors contributed equally to this work.

2

Supported by contract research “Methoden für die Lebenswissenschaften” of the Baden-Württemberg Stiftung and a personal scholarship from the Konstanz Research School Chemical Biology.