title: Eicosapentaenoic acid up-regulates apelin secretion and gene expression in 3T3-L1 adipocytes.
abstract: Recent studies have shown the ability of apelin to restore glucose tolerance in obese and insulin-resistant mice. Eicosapentaenoic acid (EPA) is a polyunsaturated fatty acid (PUFA) from the omega-3 family that has many beneficial effects in obesity-linked disorders. The aim of this study was to examine in vitro the effects of EPA on apelin secretion and gene expression in mature 3T3-L1 adipocytes. Treatment with EPA (100 and 200 microM) significantly increased basal (p<0.01) and insulin-stimulated (p<0.001) apelin secretion and gene expression in adipocytes. EPA also stimulated Akt phosphorylation, a down-stream target of phosphatidylinositol 3-kinase (PI3K), in 3T3-L1 adipocytes. Moreover, treatment with the PI3K inhibitor LY294002 completely blocked EPA-stimulatory action on apelin mRNA gene expression (p<0.001), but not modified the stimulatory effect of EPA on basal apelin secretion. Furthermore, the stimulatory effect of EPA on basal apelin release was also observed in the presence of Actinomycin D and Cycloheximide, suggesting that EPA might also regulate apelin secretion by via post-transcriptional mechanisms. These findings suggest that the mechanisms mediating EPA-induced apelin synthesis and/or secretion are complex, involving steps that are PI3K dependent and steps that are PI3K independent.
authors.affiliation: Department of Nutrition, Food Science, Physiology and Toxicology, University of Navarra, Pamplona, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lorente-Cebrián
authors.forename: Matilde
authors.initials: M
authors.lastname: Bustos
authors.forename: Amelia
authors.initials: A
authors.lastname: Marti
authors.forename: José Alfredo
authors.initials: JA
authors.lastname: Martinez
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Moreno-Aliaga
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000502:physiology*; D054392:Adipokines; D000818:Animals; D000073861:Apelin; D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003513:Cycloheximide / Q000494:pharmacology; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005786:Gene Expression Regulation; D036341:Intercellular Signaling Peptides and Proteins; D051379:Mice; D016133:Polymerase Chain Reaction / Q000379:methods; D012313:RNA / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics
chemical_list: D054392:Adipokines; D000073861:Apelin; C402826:Apln protein, mouse; D002352:Carrier Proteins; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D012313:RNA; D003513:Cycloheximide; D015118:Eicosapentaenoic Acid