Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

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Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid

Chandak, PG; Radovíc, B; Aflaki, E; Kolb, D; Buchebner, M; Fröehlich, E; Magnes, C; Sinner, F; Haemmerle, G; Zechner, R; Tabas, I; Levak-Frank, S; Kratky, D.
Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase.
J Biol Chem. 2010; 285(26): 20192-20201. [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Autor/innen der Med Uni Graz:
Aflaki Elma
Buchebner Marlene
Chandak Prakash Gopal Das
Fröhlich Eleonore
Kolb-Lenz Dagmar
Kratky Dagmar
Levak Sanja
Radovic Branislav

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Plum Analytics:
Number of Figures: 9
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Macrophage phagocytosis is an essential biological process in host defense and requires large amounts of energy. To date, glucose is believed to represent the prime substrate for ATP production in macrophages. To investigate the relative contribution of free fatty acids (FFAs) in this process, we determined the phagocytosis rates in normal mouse macrophages and macrophages of adipose triglyceride lipase (ATGL)-deficient mice. ATGL was shown to be the rate-limiting enzyme for the hydrolysis of lipid droplet-associated triacylglycerol (TG) in many tissues. Here, we demonstrate that Atgl(-/-) macrophages fail to efficiently hydrolyze cellular TG stores leading to decreased cellular FFA concentrations and concomitant accumulation of lipid droplets, even in the absence of exogenous lipid loading. The reduced availability of FFAs results in decreased cellular ATP concentrations and impaired phagocytosis suggesting that fatty acids must first go through a cycle of esterification and re-hydrolysis before they are available as energy substrate. Exogenously added glucose cannot fully compensate for the phagocytotic defect in Atgl(-/-) macrophages. Hence, phagocytosis was also decreased in vivo when Atgl(-/-) mice were challenged with bacterial particles. These findings imply that phagocytosis in macrophages depends on the availability of FFAs and that ATGL is required for their hydrolytic release from cellular TG stores. This novel mechanism links ATGL-mediated lipolysis to macrophage function in host defense and opens the way to explore possible roles of ATGL in immune response, inflammation, and atherosclerosis.
Find related publications in this database (using NLM MeSH Indexing)
Adenosine Diphosphate - metabolism
Adenosine Triphosphate - metabolism
Animals -
Blotting, Western -
Carboxylic Ester Hydrolases - genetics
Cell Line -
Cells, Cultured -
Escherichia coli - physiology
Fatty Acids, Nonesterified - metabolism
Foam Cells - cytology
Gene Expression -
Genes, Mitochondrial - genetics
Humans -
Hydrolysis -
Lipase -
Lipid Metabolism -
Macrophages - cytology
Mice -
Mice, Inbred C57BL -
Mice, Knockout -
Microscopy, Electron -
Phagocytosis - physiology
Reverse Transcriptase Polymerase Chain Reaction -
Triglycerides - metabolism

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