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Cited by 163Lipid metabolism and biosynthesisLipid metabolism and disordersFatty Acid Research and Health

Efficient Phagocytosis Requires Triacylglycerol Hydrolysis by Adipose Triglyceride Lipase

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Chandak, Prakash G., Radović, Branislav, Aflaki, Elma, Kolb, Dagmar, Buchebner, Marlene, Fröhlich, Eleonore, Magnes, Christoph, Sinner, Frank +5 more·2010·Journal of Biological Chemistry
DOI 10.1074/jbc.m110.107854PMC PMC2888432
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Abstract

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.

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  • The phagocytic function of macrophages is dependent on FFAs generated upon degradation of lipid droplets, suggesting that lipid droplet accumulation limits the phagocytic capacity of tissue-resident macrophages.

    “the phagocytic function of macrophages was found dependent on FFAs generated upon degradation of LDs, suggesting that LD accumulation somehow limits the phagocytic capacity of tissue-resident macrophages81.”

    From Amyloid-β induces lipid droplet-mediated microglial dysfunction via the enzyme DGAT2 in Alzheimer’s disease (2025) · cites this paper as [81]

    The Introduction and Discussion report that reduced release of fatty acids from lipid-droplet triglycerides impairs phagocytosis, and suggest that accumulated droplets may also contribute. But the Experimental Procedures describe thioglycollate-elicited mouse peritoneal macrophages and bone-marrow-derived macrophages; the paper does not establish the proposed limitation across tissue-resident macrophages generally. (LLM, conf=0.85)

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  • Lipid-associated macrophages control metabolic homeostasis in a TREM2 dependent manner and are transcriptionally similar to DAM.

    “Likewise, LDAM showed only low overlap with the transcriptome of recently identified “lipid-associated macrophages” from mouse and human adipose tissue, a cell population that controls metabolic homeostasis in a TREM2 dependent manner and is transcriptionally similar to DAM48.”

    From Lipid-droplet-accumulating microglia represent a dysfunctional and proinflammatory state in the aging brain (2020) · cites this paper as [48]

    The Results discuss ATGL expression in macrophages and foam cells, while the Introduction and Discussion focus on lipid storage and phagocytosis (page numbers unavailable). Searches for TREM2-dependent metabolic homeostasis and transcriptional similarity to DAM found no passage addressing either claim. (LLM, conf=0.75)

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Authors
Chandak, P. G., Radović, B., Aflaki, E., Kolb, D., Buchebner, M., Fröhlich, E., Magnes, C., Sinner, F., Haemmerle, G., Zechner, R., Tabas, I., Levak-Frank, S., & Kratky, D.
Affiliations
  • Medical University of Graz (AT)
  • University of Graz (AT)
  • Joanneum Research (AT)
  • Columbia University (US)
Corresponding author
Kratky, Dagmar
ORCID
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2010-06
Volume
285
Issue
26
Pages
20192-20201
ISSN
0021-9258 (ISSN-L)
DOI
10.1074/jbc.m110.107854
PMC
PMC2888432
OpenAlex
W2038767323
Cited by
163
References
2
Citations by year
2026: 10 · 2025: 21 · 2024: 4 · 2023: 11 · 2022: 16 · 2021: 13 · 2020: 9 · 2019: 5 · 2018: 10 · 2017: 10 · 2016: 8 · 2015: 7 · 2014: 9 · 2013: 5 · 2012: 9
FWCI
4.66
Type
journal article
Language
en
Open access
Licence
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
Funders
National Heart, Lung, and Blood Institute (HL-75662, P01HL054591, R01HL075662, HL 54591)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
Keywords
macrophage phagocytosis, adipose triglyceride lipase, lipolysis, free fatty acids, lipid droplets, ATP production, energy metabolism, glucose utilization, bacterial clearance, host defense
MeSH terms
Acyltransferases, Adenosine Diphosphate, Adenosine Triphosphate, Animals, Carboxylic Ester Hydrolases, Cell Line, Cells, Cultured, Escherichia coli, Fatty Acids, Nonesterified, Foam Cells, Humans, Hydrolysis, Lipase, Macrophages, Mice, Inbred C57BL, Microscopy, Electron, Phagocytosis, Triglycerides, Blotting, Western, Gene Expression, Mice, Knockout, Reverse Transcriptase Polymerase Chain Reaction, Genes, Mitochondrial, Lipid Metabolism, Mice

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