Author, as appears in the article.: Joan Vendrell; Sylviane Lagarrigue; Isabel C. Lopez-Mejia; Pierre-Damien Denechaud; Xavier Escoté; Judit Castillo-Armengol; Veronica Jimenez; Carine Chavey; Albert Giralt; Qiuwen Lai; Lianjun Zhang; Laia Martinez-Carreres; Brigitte Delacuisine; Jean-Sébastien Annicotte; Emilie Blanchet; Sébastien Huré; Anna Abella; Francisco J. Tinahones; Pierre Dubus; Fatima Bosch; C. Ronald Kahn; Lluis Fajas
Department: Medicina i Cirurgia
e-ISSN: 1558-8238
URV's Author/s: VENDRELL ORTEGA, JUAN JOSÉ
Keywords: Insulin Adipocyte adipogenesis
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.
Research group: Grup de Recerca Biomèdica HJ23
Thematic Areas: Ciències de la salut Ciencias de la salud Health sciences
licence for use: https://creativecommons.org/licenses/by/3.0/es/
ISSN: 0021-9738
Record's date: 2016-07-27
Last page: 348
Journal volume: 126
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/
Article's DOI: https://doi.org/10.1172/JCI81480
Entity: Universitat Rovira i Virgili
Journal publication year: 2016
First page: 335
Publication Type: Article Artículo Article