title: Microparticles release by adipocytes act as "find-me" signals to promote macrophage migration.
abstract: Macrophage infiltration of adipose tissue during weight gain is a central event leading to the metabolic complications of obesity. However, what are the mechanisms attracting professional phagocytes to obese adipose tissue remains poorly understood. Here, we demonstrate that adipocyte-derived microparticles (MPs) are critical "find-me" signals for recruitment of monocytes and macrophages. Supernatants from stressed adipocytes stimulated the attraction of monocyte cells and primary macrophages. The activation of caspase 3 was required for release of these signals. Adipocytes exposed to saturated fatty acids showed marked release of MPs into the supernatant while common genetic mouse models of obesity demonstrate high levels of circulating adipocyte-derived MPs. The release of MPs was highly regulated and dependent on caspase 3 and Rho-associated kinase. Further analysis identified these MPs as a central chemoattractant in vitro and in vivo. In addition, intravenously transplanting circulating MPs from the ob/ob mice lead to activation of monocytes in circulation and adipose tissue of the wild type mice. These data identify adipocyte-derived MPs as novel "find me" signals that contributes to macrophage infiltration associated with obesity.
authors: Department of Pediatrics, University of California San Diego (UCSD), La Jolla, California, United States of America.
authors: Akiko
authors: A
authors: Eguchi
authors: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Anny
authors: A
authors: Mulya
authors: Department of Pediatrics, University of California San Diego (UCSD), La Jolla, California, United States of America.
authors: Milos
authors: M
authors: Lazic
authors: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Deepa
authors: D
authors: Radhakrishnan
authors: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Michael P
authors: MP
authors: Berk
authors: Department of Pediatrics, University of California San Diego (UCSD), La Jolla, California, United States of America.
authors: Davide
authors: D
authors: Povero
authors: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Agnieszka
authors: A
authors: Gornicka
authors: Department of Pediatrics, University of California San Diego (UCSD), La Jolla, California, United States of America; Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Ariel E
authors: AE
authors: Feldstein
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000818:Animals; D053148:Caspase 3 / Q000378:metabolism; D002465:Cell Movement; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D002630:Chemotactic Factors / Q000378:metabolism; D002633:Chemotaxis; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D020738:Leptin / Q000502:physiology*; D017737:Macrophages, Peritoneal / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000473:pathology*; D010586:Phagocytes / Q000378:metabolism; D054460:rho-Associated Kinases / Q000378:metabolism
chemical_list: D002630:Chemotactic Factors; D020738:Leptin; D054460:rho-Associated Kinases; D053148:Caspase 3