Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity

Herms, Albert, Bosch, Marta, Ariotti, Nicholas, Reddy, Babu J. N., Fajardo, Alba, Fernandez-Vidal, Andrea, Alvarez-Guaita, Anna, Fernandez-Rojo, Manuel Alejandro, Rentero, Carles, Tebar, Francesc, Enrich, Carlos, Geli, Maria-Isabel, Parton, Robert G., Gross, Steven P. and Pol, Albert (2013) Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity. Current Biology, 23 15: 1489-1496. doi:10.1016/j.cub.2013.06.032


Author Herms, Albert
Bosch, Marta
Ariotti, Nicholas
Reddy, Babu J. N.
Fajardo, Alba
Fernandez-Vidal, Andrea
Alvarez-Guaita, Anna
Fernandez-Rojo, Manuel Alejandro
Rentero, Carles
Tebar, Francesc
Enrich, Carlos
Geli, Maria-Isabel
Parton, Robert G.
Gross, Steven P.
Pol, Albert
Title Cell-to-cell heterogeneity in lipid droplets suggests a mechanism to reduce lipotoxicity
Journal name Current Biology   Check publisher's open access policy
ISSN 0960-9822
1879-0445
Publication date 2013-08-01
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.cub.2013.06.032
Open Access Status Not yet assessed
Volume 23
Issue 15
Start page 1489
End page 1496
Total pages 8
Place of publication Cambridge, MA, United States
Publisher Cell Press
Language eng
Subject 1300 Biochemistry, Genetics and Molecular Biology
1100 Agricultural and Biological Sciences
Abstract Lipid droplets (LDs) are dynamic organelles that collect, store, and supply lipids [1]. LDs have a central role in the exchange of lipids occurring between the cell and the environment and provide cells with substrates for energy metabolism, membrane synthesis, and production of lipid-derived molecules such as lipoproteins or hormones. However, lipid-derived metabolites also cause progressive lipotoxicity [2], accumulation of reactive oxygen species (ROS), endoplasmic reticulum stress, mitochondrial malfunctioning, and cell death [2]. Intracellular accumulation of LDs is a hallmark of prevalent human diseases, including obesity, steatosis, diabetes, myopathies, and arteriosclerosis [3]. Indeed, nonalcoholic fatty liver disease is the most common cause of abnormal hepatic function among adults [4, 5]. Lipotoxicity gradually promotes cellular ballooning and disarray, megamitochondria, accumulation of Mallory's hyaline in hepatocytes, and inflammation, fibrosis, and cirrhosis in the liver. Here, using confocal microscopy, serial-block-face scanning electron microscopy, and flow cytometry, we show that LD accumulation is heterogeneous within a cell population and follows a positive skewed distribution. Lipid availability and fluctuations in biochemical networks controlling lipolysis, fatty acid oxidation, and protein synthesis contribute to cell-to-cell heterogeneity. Critically, this reversible variability generates a subpopulation of cells that effectively collect and store lipids. This high-lipid subpopulation accumulates more LDs and more ROS and reduces the risk of lipotoxicity to the population without impairing overall lipid homeostasis, since high-lipid cells can supply stored lipids to the other cells. In conclusion, we demonstrate fat storage compartmentalization within a cell population and propose that this is a protective social organization to reduce lipotoxicity.
Formatted abstract
Lipid droplets (LDs) are dynamic organelles that collect, store, and supply lipids [1]. LDs have a central role in the exchange of lipids occurring between the cell and the environment and provide cells with substrates for energy metabolism, membrane synthesis, and production of lipid-derived molecules such as lipoproteins or hormones. However, lipid-derived metabolites also cause progressive lipotoxicity [2], accumulation of reactive oxygen species (ROS), endoplasmic reticulum stress, mitochondrial malfunctioning, and cell death [2]. Intracellular accumulation of LDs is a hallmark of prevalent human diseases, including obesity, steatosis, diabetes, myopathies, and arteriosclerosis [3]. Indeed, nonalcoholic fatty liver disease is the most common cause of abnormal hepatic function among adults [4, 5]. Lipotoxicity gradually promotes cellular ballooning and disarray, megamitochondria, accumulation of Mallory's hyaline in hepatocytes, and inflammation, fibrosis, and cirrhosis in the liver. Here, using confocal microscopy, serial-block-face scanning electron microscopy, and flow cytometry, we show that LD accumulation is heterogeneous within a cell population and follows a positive skewed distribution. Lipid availability and fluctuations in biochemical networks controlling lipolysis, fatty acid oxidation, and protein synthesis contribute to cell-to-cell heterogeneity. Critically, this reversible variability generates a subpopulation of cells that effectively collect and store lipids. This high-lipid subpopulation accumulates more LDs and more ROS and reduces the risk of lipotoxicity to the population without impairing overall lipid homeostasis, since high-lipid cells can supply stored lipids to the other cells. In conclusion, we demonstrate fat storage compartmentalization within a cell population and propose that this is a protective social organization to reduce lipotoxicity.
Keyword Fatty liver disease
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID BFU2011-23745
GM64624/NIH
BFU2009-13526
BFU2009-10335
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
Centre for Microscopy and Microanalysis Publications
 
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