Articles producció científica> Medicina i Cirurgia

CDK4 is an essential insulin effector in adipocytes

  • Identification data

    Identifier: imarina:6458102
    Authors:
    Lagarrigue SLopez-Mejia ICDenechaud PDEscoté XCastillo-Armengol JJimenez VChavey CGiralt ALai QZhang LMartinez-Carreres LDelacuisine BAnnicotte JSBlanchet EHuré SAbella ATinahones FJVendrell JDubus PBosch FKahn CRFajas L
    Abstract:
    Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.
  • Others:

    Author, as appears in the article.: Lagarrigue S; Lopez-Mejia IC; Denechaud PD; Escoté X; Castillo-Armengol J; Jimenez V; Chavey C; Giralt A; Lai Q; Zhang L; Martinez-Carreres L; Delacuisine B; Annicotte JS; Blanchet E; Huré S; Abella A; Tinahones FJ; Vendrell J; Dubus P; Bosch F; Kahn CR; Fajas L
    Department: Medicina i Cirurgia
    URV's Author/s: Escote Miro, Xavier / Vendrell Ortega, Juan José
    Keywords: Transcription Promotes adipogenesis Mice Metabolism Mediated phosphorylation Insulin Inhibition Cell-cycle Cancer Adipose-tissue Adipogenesis Adipocyte Activation
    Abstract: Insulin resistance is a fundamental pathogenic factor that characterizes various metabolic disorders, including obesity and type 2 diabetes. Adipose tissue contributes to the development of obesity-related insulin resistance through increased release of fatty acids, altered adipokine secretion, and/or macrophage infiltration and cytokine release. Here, we aimed to analyze the participation of the cyclin-dependent kinase 4 (CDK4) in adipose tissue biology. We determined that white adipose tissue (WAT) from CDK4-deficient mice exhibits impaired lipogenesis and increased lipolysis. Conversely, lipolysis was decreased and lipogenesis was increased in mice expressing a mutant hyperactive form of CDK4 (CDK4R24C). A global kinome analysis of CDK4-deficient mice following insulin stimulation revealed that insulin signaling is impaired in these animals. We determined that insulin activates the CCND3-CDK4 complex, which in turn phosphorylates insulin receptor substrate 2 (IRS2) at serine 388, thereby creating a positive feedback loop that maintains adipocyte insulin signaling. Furthermore, we found that CCND3 expression and IRS2 serine 388 phosphorylation are increased in human obese subjects. Together, our results demonstrate that CDK4 is a major regulator of insulin signaling in WAT.
    Thematic Areas: Saúde coletiva Odontología Medicine, research & experimental Medicine (miscellaneous) Medicine (all) Medicina veterinaria Medicina ii Medicina i Interdisciplinar General medicine Farmacia Educação física Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Biotecnología
    licence for use: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 00219738
    Author's mail: xavier.escote@urv.cat juanjose.vendrell@urv.cat
    Author identifier: 0000-0003-1172-3995 0000-0002-6994-6115
    Record's date: 2024-09-07
    Papper version: info:eu-repo/semantics/publishedVersion
    Link to the original source: https://www.jci.org/articles/view/81480
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Journal Of Clinical Investigation. 126 (1): 335-348
    APA: Lagarrigue S; Lopez-Mejia IC; Denechaud PD; Escoté X; Castillo-Armengol J; Jimenez V; Chavey C; Giralt A; Lai Q; Zhang L; Martinez-Carreres L; Delacui (2016). CDK4 is an essential insulin effector in adipocytes. Journal Of Clinical Investigation, 126(1), 335-348. DOI: 10.1172/JCI81480
    Article's DOI: 10.1172/JCI81480
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2016
    Publication Type: Journal Publications
  • Keywords:

    Medicine (Miscellaneous),Medicine, Research & Experimental
    Transcription
    Promotes adipogenesis
    Mice
    Metabolism
    Mediated phosphorylation
    Insulin
    Inhibition
    Cell-cycle
    Cancer
    Adipose-tissue
    Adipogenesis
    Adipocyte
    Activation
    Saúde coletiva
    Odontología
    Medicine, research & experimental
    Medicine (miscellaneous)
    Medicine (all)
    Medicina veterinaria
    Medicina ii
    Medicina i
    Interdisciplinar
    General medicine
    Farmacia
    Educação física
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Biotecnología
  • Documents:

  • Cerca a google

    Search to google scholar