title: Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes.
abstract: Fas (CD95) is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in the induction of apoptosis. However, like TNF, Fas can induce nonapoptotic signaling pathways. We previously demonstrated that mice lacking Fas specifically in adipocytes are partly protected from diet-induced insulin resistance, potentially via decreased delivery of FAs to the liver, as manifested by lower total liver ceramide content. In the present study, we aimed to delineate the signaling pathway involved in Fas-mediated adipocyte lipid mobilization. Treatment of differentiated 3T3-L1 adipocytes with membrane-bound Fas ligand (FasL) significantly increased lipolysis after 12 h without inducing apoptosis. In parallel, Fas activation increased phosphorylation of ERK1/2, and FasL-induced lipolysis was blunted in the presence of the ERK-inhibitor U0126 or in ERK1/2-depleted adipocytes. Furthermore, Fas activation increased phosphorylation of the Ca(2+)/calmodulin-dependent protein kinases II (CaMKII), and blocking of the CaMKII-pathway (either by the Ca(2+) chelator BAPTA or by the CaMKII inhibitor KN62) blunted FasL-induced ERK1/2 phosphorylation and glycerol release. In conclusion, we propose a novel role for CaMKII in promoting lipolysis in adipocytes.
authors.affiliation: Division of Pediatric Endocrinology and Diabetology, University Children's Hospital, CH-8032 Zurich, Switzerland.
authors.forename: Reto A
authors.initials: RA
authors.lastname: Rapold
authors.forename: Stephan
authors.initials: S
authors.lastname: Wueest
authors.forename: Adrian
authors.initials: A
authors.lastname: Knoepfel
authors.forename: Eugen J
authors.initials: EJ
authors.lastname: Schoenle
authors.forename: Daniel
authors.initials: D
authors.lastname: Konrad
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D006868:Hydrolysis; D042541:Intracellular Space / Q000378:metabolism; D008066:Lipolysis; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D002787:Sterol Esterase / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
chemical_list: D014280:Triglycerides; D019014:fas Receptor; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D002787:Sterol Esterase