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J Lipid Res. 2016 Jun;57(6):980-92. doi: 10.1194/jlr.M064089. Epub 2016 Apr 4.

Exocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation.

Author information

1
Departments of Biochemistry, Weill Cornell Medical College, New York, NY 10065.
2
Medicine, Weill Cornell Medical College, New York, NY 10065.
3
Pathology and Laboratory Medicine, Weill Cornell Medical College, New York, NY 10065.
4
Medicine, Weill Cornell Medical College, New York, NY 10065 Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY 10065.
5
Departments of Biochemistry, Weill Cornell Medical College, New York, NY 10065 frmaxfie@med.cornell.edu.

Abstract

Many types of apoptotic cells are phagocytosed and digested by macrophages. Adipocytes can be hundreds of times larger than macrophages, so they are too large to be digested by conventional phagocytic processes. The nature of the interaction between macrophages and apoptotic adipocytes has not been studied in detail. We describe a cellular process, termed exophagy, that is important for macrophage clearance of dead adipocytes and adipose tissue homeostasis. Using mouse models of obesity, human tissue, and a cell culture model, we show that macrophages form hydrolytic extracellular compartments at points of contact with dead adipocytes using local actin polymerization. These compartments are acidic and contain lysosomal enzymes delivered by exocytosis. Uptake and complete degradation of adipocyte fragments, which are released by extracellular hydrolysis, leads to macrophage foam cell formation. Exophagy-mediated foam cell formation is a highly efficient means by which macrophages internalize large amounts of lipid, which may ultimately overwhelm the metabolic capacity of the macrophage. This process provides a mechanism for degradation of objects, such as dead adipocytes, that are too large to be phagocytosed by macrophages.

KEYWORDS:

adipose tissue; crown-like structure; extracellular catabolism; lipolysis and fatty acid metabolism; obesity

PMID:
27044658
PMCID:
PMC4878183
DOI:
10.1194/jlr.M064089
[Indexed for MEDLINE]
Free PMC Article

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