Autor según el artículo: Ceperuelo-Mallafre, Victoria; Ejarque, Miriam; Duran, Xavier; Pachon, Gisela; Vazquez-Carballo, Ana; Roche, Kelly; Nunez-Roa, Catalina; Garrido-Sanchez, Lourdes; Tinahones, Francisco J.; Vendrell, Joan; Fernandez-Veledo, Sonia;
Departamento: Ciències Mèdiques Bàsiques Medicina i Cirurgia
Autor/es de la URV: Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
Palabras clave: Zinc-alpha(2)-glycoprotein Weight Skeletal-muscle Resistance Pathways Necrosis-factor-alpha Lipolysis Lipid mobilizing factor Glucose-uptake Adipose-tissue
Resumen: Objective: Evidence from mouse models suggests that zinc-α2-glycoprotein (ZAG) is a novel anti-obesity adipokine. In humans, however, data are controversial and its physiological role in adipose tissue (AT) remains unknown. Here we explored the molecular mechanisms by which ZAG regulates carbohydrate metabolism in human adipocytes. Methods: ZAG action on glucose uptake and insulin action was analyzed. β1 and β2-adrenoreceptor (AR) antagonists and siRNA targeting PP2A phosphatase were used to examine the mechanisms by which ZAG modulates insulin sensitivity. Plasma levels of ZAG were measured in a lean patient cohort stratified for HOMA-IR. Results: ZAG treatment increased basal glucose uptake, correlating with an increase in GLUT expression, but induced insulin resistance in adipocytes. Pretreatment of adipocytes with propranolol and a specific β1-AR antagonist demonstrated that ZAG effects on basal glucose uptake and GLUT4 expression are mediated via β1-AR, whereas inhibition of insulin action is dependent on β2-AR activation. ZAG treatment correlated with an increase in PP2A activity. Silencing of the PP2A catalytic subunit abrogated the negative effect of ZAG on insulinstimulated AKT phosphorylation and glucose uptake but not on GLUT4 expression and basal glucose uptake. ZAG circulating levels were unchanged in a lean patient cohort stratified for HOMA-IR. Neither glucose nor insulin was associated with plasma ZAG. Conclusions: ZAG inhibits insulin-induced glucose uptake in human adipocytes by impairing insulin signaling at the level of AKT in a β2-AR- and PP2A-dependent manner. © 2015 Ceperuelo-Mallafré et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Áreas temáticas: Zootecnia / recursos pesqueiros Sociology Sociología Serviço social Saúde coletiva Química Psychology Psicología Planejamento urbano e regional / demografia Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicine (miscellaneous) Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Linguística e literatura Letras / linguística Interdisciplinary research in the social sciences Interdisciplinar Human geography and urban studies History & philosophy of science Historia Geografía Geociências General medicine General biochemistry,genetics and molecular biology General agricultural and biological sciences Farmacia Environmental studies Ensino Engenharias iv Engenharias iii Engenharias ii Engenharias i Enfermagem Educação física Educação Economia Direito Demography Comunicação e informação Ciências sociais aplicadas i Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência política e relações internacionais Ciência de alimentos Ciência da computação Biotecnología Biology Biodiversidade Biochemistry, genetics and molecular biology (miscellaneous) Astronomia / física Arquitetura, urbanismo e design Archaeology Antropologia / arqueologia Anthropology Agricultural and biological sciences (miscellaneous) Administração, ciências contábeis e turismo Administração pública e de empresas, ciências contábeis e turismo
Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
Direcció de correo del autor: victoria.ceperuelo@urv.cat sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
Identificador del autor: 0000-0002-4460-9761 0000-0003-2906-3788 0000-0002-6994-6115
Fecha de alta del registro: 2024-09-07
Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Plos One. 10 (6): e0129644-
Referencia de l'ítem segons les normes APA: Ceperuelo-Mallafre, Victoria; Ejarque, Miriam; Duran, Xavier; Pachon, Gisela; Vazquez-Carballo, Ana; Roche, Kelly; Nunez-Roa, Catalina; Garrido-Sanche (2015). Zinc-alpha 2-Glycoprotein Modulates AKT-Dependent Insulin Signaling in Human Adipocytes by Activation of the PP2A Phosphatase. Plos One, 10(6), e0129644-. DOI: 10.1371/journal.pone.0129644
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2015
Tipo de publicación: Journal Publications
Repositori URV