title: Microvesicles released from rat adipocytes and harboring glycosylphosphatidylinositol-anchored proteins transfer RNA stimulating lipid synthesis.
abstract: Small microvesicles, such as microparticles and exosomes, have been demonstrated to transfer proteins and nucleic acids from a variety of donor to acceptor cells with corresponding (patho)physiological consequences. Recently the in vitro transfer of glycosylphosphatidylinositol (GPI)-anchored proteins from microvesicles released from large rat adipocytes to intracellular lipid droplets (LDs) of small adipocytes has been shown to be upregulated by physiological (palmitate, H(2)O(2)) and pharmacological (anti-diabetic sulfonylurea drug glimepiride) stimuli and to increase the esterification into as well as to reduce the release of fatty acids from triacylglycerol. Here microvesicles derived from (preferentially large) rat adipocytes or plasma and harboring the GPI-anchored proteins, Gce1 and CD73, were demonstrated to contain specific transcripts and microRNAs that are both transferred into and expressed in acceptor adipocytes and are involved in the upregulation of lipogenesis and cell size. The transferred transcripts were specific for fatty acid esterification (glycerol-3-phosphate acyltransferase-3, diacylglycerol acyltransferase-2), lipid droplet biogenesis (FSP27, caveolin-1) and adipokines (leptin, adiponectin). The transfer and lipogenic activity were more efficient for small rather than large acceptor adipocytes and significantly upregulated by palmitate, glimepiride and H(2)O(2). Together the data suggest that microvesicles released from large adipocytes stimulate lipid storage in small adipocytes by mediating horizontal transfer of lipogenic information which is encoded by relevant (micro)RNA and GPI-anchored protein species. Paracrine and endocrine regulation of lipid storage and, in parallel, cell size of white adipocytes by specific (micro)RNAs in GPI-anchored protein-harboring microvesicles may represent a novel target for interference with metabolic diseases, such as obesity and metabolic syndrome.
authors: Sanofi-Aventis Deutschland GmbH, R & D Diabetes, Industrial Park Höchst, Frankfurt am Main, Germany. guenter.mueller@sanofi-aventis.com
authors: Günter
authors: G
authors: Müller
authors: Marion
authors: M
authors: Schneider
authors: Gabriele
authors: G
authors: Biemer-Daub
authors: Susanne
authors: S
authors: Wied
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001808:Blood Vessels / Q000166:cytology; D002454:Cell Differentiation; D048429:Cell Size; D055252:Cell-Derived Microparticles / Q000235:genetics / Q000378:metabolism*; D004951:Esterification; D055354:Exosomes / Q000235:genetics / Q000378:metabolism*; D058851:GPI-Linked Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D010168:Palmitates / Q000494:pharmacology; D010718:Phosphatidylserines / Q000378:metabolism; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017154:Stromal Cells / Q000166:cytology; D013453:Sulfonylurea Compounds / Q000494:pharmacology; D014158:Transcription, Genetic
chemical_list: D054392:Adipokines; D058851:GPI-Linked Proteins; D008055:Lipids; D035683:MicroRNAs; D010168:Palmitates; D010718:Phosphatidylserines; D012333:RNA, Messenger; D013453:Sulfonylurea Compounds; C057619:glimepiride; D006861:Hydrogen Peroxide