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