Pulido, Marina RDíaz-Ruiz, AlbertoJiménez-Gómez, YolandaGarcía-Navarro, SocorroGracia-Navarro, FranciscoTinahones, FranciscoLópez-Miranda, JoséFrühbeck, GemaVázquez-Martínez, RafaelMalagón, María M2013-06-242013-06-242011-07-28Pulido MR, Diaz-Ruiz A, Jiménez-Gómez Y, Garcia-Navarro S, Gracia-Navarro F, Tinahones F, et al. Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity. PLoS ONE. 2011; 6(7):e22931http://hdl.handle.net/10668/1157Journal Article; Research Support, Non-U.S. Gov't;Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed.enRab18 protein, mouseAdipocitosAdiponectinaWestern BlottingCélulas CultivadasRetículo EndoplásmicoHipoglucemiantesTécnicas para InmunoenzimasMetabolismo de los LípidosObesidadReacción en Cadena de la Polimerasa de Transcriptasa InversaCélulas 3T3-L1InsulinaMedical Subject Headings::Anatomy::Cells::Connective Tissue Cells::AdipocytesMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Adipokines::AdiponectinMedical Subject Headings::Organisms::Eukaryota::AnimalsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Chemistry Techniques, Analytical::Electrophoresis::Blotting, WesternMedical Subject Headings::Anatomy::Cells::Cells, CulturedMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Endoplasmic ReticulumMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Hypoglycemic AgentsMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Immunologic Techniques::Immunoassay::Immunoenzyme TechniquesMedical Subject Headings::Chemicals and Drugs::Hormones, Hormone Substitutes, and Hormone Antagonists::Hormones::Peptide Hormones::Pancreatic Hormones::InsulinsMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid MetabolismMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::LipogenesisMedical Subject Headings::Phenomena and Processes::Metabolic Phenomena::Metabolism::Lipid Metabolism::LipolysisMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Diseases::Nutritional and Metabolic Diseases::Nutrition Disorders::Overnutrition::ObesityMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::RNA::RNA, MessengerMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Genetic Techniques::Nucleic Acid Amplification Techniques::Polymerase Chain Reaction::Reverse Transcriptase Polymerase Chain ReactionMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Acid Anhydride Hydrolases::GTP Phosphohydrolases::GTP-Binding ProteinsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::3T3 Cellsresearch article21829560open access10.1371/journal.pone.00229311932-6203PMC3145781