biostudies-literatureHaka ASNCRR NIH HHSNIDDK NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNational Cancer Research InstituteNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNCI NIH HHSNational Institutes of HealthNIH HHS980-92https://www.ebi.ac.uk/biostudies/studies/S-EPMC4878183biostudies-literatureUnknown57(6)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 adiJournal of lipid researchExocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation.PMC4878183R01 CA154481R37-DK27083C06 RR017528S10 RR017291RO1-HL092234R01 HL093331R00 HL0922345R01CA154481S10 OD019994K99 HL092234R37 DK027083HL093331S10 RR029300Barbosa-Lorenzi VCFalcone DJHudis CAHaka ASMaxfield FRDannenberg AJLee HJfalseExocytosis of macrophage lysosomes leads to digestion of apoptotic adipocytes and foam cell formation.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 adi2016-01-01T00:00:00Z2016 Jun2025-04-04T07:28:02.353Z2019-03-27T02:14:25ZS-EPMC48781832704465810.1194/jlr.M064089