title: Induced release of membrane vesicles from rat adipocytes containing glycosylphosphatidylinositol-anchored microdomain and lipid droplet signalling proteins.
abstract: Synthesis and degradation of lipids in mammalian adipocytes are tightly and coordinatedly regulated by insulin, fatty acids, reactive oxygen species and drugs. Conversely, the lipogenic or lipolytic state of adipocytes is communicated to other tissues by the secretion of soluble adipocytokines. Here we report that insulin, palmitate, H(2)O(2) and the antidiabetic sulfonylurea drug glimepiride induce the release of the typical lipid droplet (LD) protein, perilipin-A, as well as typical plasma membrane microdomain (DIGs) proteins, such as caveolin-1 and the glycosylphosphatidylinositol (GPI)-anchored proteins, Gce1 and CD73 from rat adipocytes. According to biochemical and morphological criteria these LD and GPI-proteins are embedded within two different types of phospholipid-containing membrane vesicles, collectively called adiposomes. Adiposome release was not found to be causally related to cell lysis or apoptosis. The interaction of Gce1 and CD73 with the adiposomes apparently depends on their intact GPI anchor. Pull-down of caveolin-1, perilipin-A and CD73 together with phospholipids (via binding to annexin-V) as well as mutually of caveolin-1 with CD73 or perilipin-A (via coimmunoprecipitation) argues for their colocalization within the same adiposome vesicle. Taken together, certain lipogenic and anti-lipolytic agents induce the specific release of a subset of LD and DIGs proteins, including certain GPI-proteins, in adiposomes from primary rat adipocytes. Given the (c)AMP-degrading activities of Gce1 and CD73 and LD-forming function of perilipin-A and caveolin-1, the physiological relevance of the release of adiposomes from adipocytes may rely on the intercellular transfer of lipogenic and anti-lipolytic information.
authors.affiliation: Sanofi-Aventis Pharma, R & D, Therapeutic Department Metabolism, Industrial Park Höchst, Bldg. H821, 65926 Frankfurt am Main, Germany. Guenter.Mueller@sanofi-aventis.com
authors.forename: Günter
authors.initials: G
authors.lastname: Müller
authors.forename: Christian
authors.initials: C
authors.lastname: Jung
authors.forename: Julia
authors.initials: J
authors.lastname: Straub
authors.forename: Susanne
authors.initials: S
authors.lastname: Wied
authors.forename: Werner
authors.initials: W
authors.lastname: Kramer
mesh_terms: D015720:5'-Nucleotidase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D002352:Carrier Proteins; D051242:Caveolin 1 / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D055354:Exosomes / Q000502:physiology; D017261:Glycosylphosphatidylinositols / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D021962:Membrane Microdomains / Q000187:drug effects / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000378:metabolism*; D051381:Rats; D022142:Secretory Vesicles / Q000378:metabolism*; D013453:Sulfonylurea Compounds / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D002352:Carrier Proteins; D051242:Caveolin 1; D017261:Glycosylphosphatidylinositols; D008565:Membrane Proteins; D010168:Palmitates; D000070778:Perilipin-1; D010750:Phosphoproteins; D013453:Sulfonylurea Compounds; C057619:glimepiride; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D015720:5'-Nucleotidase