title: Mechanisms of Action of Compounds That Enhance Storage Lipid Accumulation in Daphnia magna.
abstract: Accumulation of storage lipids in the crustacean Daphnia magna can be altered by a number of exogenous and endogenous compounds, like 20-hydroxyecdysone (natural ligand of the ecdysone receptor, EcR), methyl farnesoate, pyrirproxyfen (agonists of the methyl farnesoate receptor, MfR), and tributyltin (agonist of the retinoid X acid receptor, RXR). This effect, analogous to the obesogenic disruption in mammals, alters Daphnia's growth and reproductive investment. Here we propose that storage lipid accumulation in droplets is regulated in Daphnia by the interaction between the nuclear receptor heterodimer EcR:RXR and MfR. The model was tested by determining changes in storage lipid accumulation and on gene transcription in animals exposed to different effectors of RXR, EcR, and MfR signaling pathways, either individually or in combination. RXR, EcR, and MfR agonists increased storage lipid accumulation, whereas fenarimol and testosterone (reported inhibitors of ecdysteroid synthesis and an EcR antagonist, respectively) decreased it. Joint effects of mixtures with fenarimol, testosterone, and ecdysone were antagonistic, mixtures of juvenoids showed additive effects following a concentration addition model, and combinations of tributyltin with juvenoids resulted in greater than additive effects. Co-exposures of ecdysone with juvenoids resulted in deregulation of ecdysone- and farnesoid-regulated genes, accordingly with the observed changes in lipid accumulation These results indicate the requirement of ecdysone binding to the EcR:RXR:MfR complex to regulate lipid storage and that an excess of ecdysone disrupts the whole process, probably by triggering negative feedback mechanisms.
authors.affiliation: Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Research Council (IDAEA, CSIC) , Jordi Girona 18, 08034 Barcelona, Spain.|Centre for Environmental and Marine studies (CESAM), Department of Biology, University of Aveiro , Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Rita
authors.initials: R
authors.lastname: Jordão
authors.affiliation: Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Research Council (IDAEA, CSIC) , Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Bruno
authors.identifier: 0000-0002-3701-4858
authors.initials: B
authors.lastname: Campos
authors.affiliation: Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Research Council (IDAEA, CSIC) , Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Benjamín
authors.initials: B
authors.lastname: Piña
authors.affiliation: Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Research Council (IDAEA, CSIC) , Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Romà
authors.initials: R
authors.lastname: Tauler
authors.affiliation: Centre for Environmental and Marine studies (CESAM), Department of Biology, University of Aveiro , Campus Universitário de Santiago, 3810-193 Aveiro, Portugal.
authors.forename: Amadeu M V M
authors.initials: AM
authors.lastname: Soares
authors.affiliation: Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research (IDAEA), Spanish Research Council (IDAEA, CSIC) , Jordi Girona 18, 08034 Barcelona, Spain.
authors.forename: Carlos
authors.identifier: 0000-0002-3360-0729
authors.initials: C
authors.lastname: Barata
mesh_terms: D000818:Animals; D003621:Daphnia / Q000187:drug effects*; D008024:Ligands; D012098:Reproduction; D047488:Retinoid X Receptors; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D008024:Ligands; D047488:Retinoid X Receptors; D014157:Transcription Factors