Tributyltin impacts in metabolic syndrome development through disruption of angiotensin II receptor signaling pathways in white adipose tissue from adult female rats

dc.contributor.authorCeotto Freitas-Lima, Leandro
dc.contributor.authorMerlo, Eduardo
dc.contributor.authorCampos Zicker, Marina
dc.contributor.authorNavia-Pelaez, Juliana Maria
dc.contributor.authorde Oliveira, Miriane
dc.contributor.authordos Santos Aggum Capettini, Luciano
dc.contributor.authorNogueira, Célia Regina
dc.contributor.authorVersiani Matos Ferreira, Adaliene
dc.contributor.authorSousa Santos, Sérgio Henrique
dc.contributor.authorBernardes Graceli, Jones
dc.contributor.institutionFederal University of Espírito Santo
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Federal do Espírito Santo (UFES)
dc.description.abstractWhite adipose tissue (WAT) dysfunction and obesity are a consequence of a low-grade inflammation state. These WAT irregularities could result from abnormal metabolic renin-angiotensin system (RAS) control. Recently, tributyltin (TBT) has been found to play a critical role in these metabolic irregularities. However, TBT actions on the WAT-RAS functions are not currently well understood. In this study, we assessed whether TBT exposure resulted in metabolic syndrome (MetS) development and other metabolic complications as a result of abnormal modulation of WAT-RAS pathways. TBT (100 ng/kg/day) was administered to adult female Wistar rats, and their WAT morphophysiology and adipokine profiles were assessed. We further assessed the expression of Angiotensin-II receptor proteins (AT1R and AT2R) and proteins involved in downstream pathways mediating inflammation and adipogenesis modulation. TBT-exposed rats exhibited increases in body weight and adiposity. TBT rats present dyslipidemia and insulin resistance, suggesting MetS development. TBT promoted WAT inflammatory infiltration, AT1R protein overexpression and reduced Angiotensin-(1–7) expression. These TBT WAT abnormalities are reflected by NFκB activation, with higher adipokine levels (leptin, TNF-α and IL-6) and overexpression of AKT, ERK, P38, FAS and PPARγ protein. In vitro, TBT exposure stimulates lipid accumulation, reduces AT2R protein expression, and increases leptin, AKT and ERK protein expression in 3T3L1 cells. These findings suggest that TBT exposure participates in MetS development via the improper function of WAT-RAS metabolic control.en
dc.description.affiliationDepartment of Morphology Healthy Sciences Center Federal University of Espírito Santo
dc.description.affiliationDepartment. of Food Science Faculty of Pharmacy Federal University of Minas Gerais
dc.description.affiliationDepartment of Pharmacology Biological Sciences Institute Federal University of Minas Gerais
dc.description.affiliationDepartment of Internal Medicine Botucatu School of Medicine University of São Paulo State
dc.description.affiliationDept. of Basic Nursing Nursing School Federal University of Minas Gerais
dc.description.affiliationHealth Science Graduate Program UNIMONTES
dc.description.affiliationInstitute of Agricultural Sciences Food Engineering College Federal University of Minas Gerais
dc.description.affiliationLaboratório de Endocrinologia e Toxicologia Celular Programa de Pós-Graduação em Ciências Fisiológicas/CCS Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468, Prédio do básico I, sala 5
dc.identifier.citationToxicology Letters, v. 299, p. 21-31.
dc.relation.ispartofToxicology Letters
dc.subjectMetabolic syndrome
dc.subjectTributyltin chloride
dc.titleTributyltin impacts in metabolic syndrome development through disruption of angiotensin II receptor signaling pathways in white adipose tissue from adult female ratsen