Articles producció científica> Medicina i Cirurgia

Zinc-alpha 2-Glycoprotein Modulates AKT-Dependent Insulin Signaling in Human Adipocytes by Activation of the PP2A Phosphatase

  • Identification data

    Identifier: imarina:5130456
    Authors:
    Ceperuelo-Mallafre, VictoriaEjarque, MiriamDuran, XavierPachon, GiselaVazquez-Carballo, AnaRoche, KellyNunez-Roa, CatalinaGarrido-Sanchez, LourdesTinahones, Francisco J.Vendrell, JoanFernandez-Veledo, Sonia
    Abstract:
    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 repr
  • Others:

    Author, as appears in the article.: 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;
    Department: Ciències Mèdiques Bàsiques Medicina i Cirurgia
    URV's Author/s: Ceperuelo Mallafré, Maria Victoria / Fernandez Veledo, Sonia / Vendrell Ortega, Juan José
    Keywords: Zinc-alpha(2)-glycoprotein Weight Skeletal-muscle Resistance Pathways Necrosis-factor-alpha Lipolysis Lipid mobilizing factor Glucose-uptake Adipose-tissue
    Abstract: 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.
    Thematic Areas: 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
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    Author's mail: victoria.ceperuelo@urv.cat sonia.fernandez@urv.cat juanjose.vendrell@urv.cat
    Author identifier: 0000-0002-4460-9761 0000-0003-2906-3788 0000-0002-6994-6115
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0129644
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Plos One. 10 (6): e0129644-
    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
    Article's DOI: 10.1371/journal.pone.0129644
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2015
    Publication Type: Journal Publications
  • Keywords:

    Agricultural and Biological Sciences (Miscellaneous),Biochemistry, Genetics and Molecular Biology (Miscellaneous),Biology,Medicine (Miscellaneous),Multidisciplinary,Multidisciplinary Sciences
    Zinc-alpha(2)-glycoprotein
    Weight
    Skeletal-muscle
    Resistance
    Pathways
    Necrosis-factor-alpha
    Lipolysis
    Lipid mobilizing factor
    Glucose-uptake
    Adipose-tissue
    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 turism
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