title: Fatty acids increase adiponectin secretion through both classical and exosome pathways.
abstract: Little is known about the effects of fatty acids on adiponectin oligomer assembly and trafficking. The aim of this study was to examine the effects of different fatty acids on adiponectin transport and secretion in differentiated 3T3-L1 adipocytes. Subcellular fractionation and immunofluorescence microscopy revealed that the majority of cellular adiponectin was located in the endoplasmic reticulum (ER). Adiponectin secretion was increased by treatment with fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and several fatty acids changed the cellular localization of adiponectin. Adiponectin secretion has been shown to be altered by ER stress and interactions with ER chaperone proteins. However these mechanisms were not influenced by fatty acids, suggesting that alternative mechanisms must be responsible for the increased secretion of adiponectin observed with fatty acid treatment. Secretion of adiponectin was blocked by Brefeldin A, but we identified a minor pool of adiponectin that could be secreted from beyond the Brefeldin A block. Exosomes appeared to contribute to a minor amount of adiponectin secreted from the cell, and exosome release was increased by treatment with DHA. These data suggest that the ER is an important site of adiponectin accumulation and that treatment with long chain omega-3 fatty acids increases adiponectin release. Furthermore, the secretory pathway of adiponectin is complex, involving both the classical ER-Golgi pathway as well as unconventional secretory mechanisms such as an exosome-mediated pathway.
authors.affiliation: Dept. of Biochemistry & Molecular Biology, Dalhousie University, Rm. 9C, Sir Charles Tupper Medical Bldg., 5850 College Street, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Vanessa
authors.initials: V
authors.lastname: DeClercq
authors.affiliation: Dept. of Biochemistry & Molecular Biology, Dalhousie University, Rm. 9C, Sir Charles Tupper Medical Bldg., 5850 College Street, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada.
authors.forename: Brandon
authors.initials: B
authors.lastname: d'Eon
authors.affiliation: Dept. of Biochemistry & Molecular Biology, Dalhousie University, Rm. 9C, Sir Charles Tupper Medical Bldg., 5850 College Street, PO Box 15000, Halifax, Nova Scotia B3H 4R2, Canada. Electronic address: rmcleod2@dal.ca.
authors.forename: Roger S
authors.initials: RS
authors.lastname: McLeod
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D020126:Brefeldin A / Q000494:pharmacology; D002454:Cell Differentiation; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism; D055354:Exosomes / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression; D006056:Golgi Apparatus / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D052242:Adiponectin; C499919:Adipoq protein, mouse; D018832:Molecular Chaperones; D020126:Brefeldin A; D004281:Docosahexaenoic Acids; D015118:Eicosapentaenoic Acid
keywords: Adipocytes; Adiponectin; Fatty acids; Oligomer assembly; Secretory pathway