Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance

• DOI: 10.1038/s41467-017-02074-2
• Publication Date: 2017-11-22T13:37:11Z
• Authors: Xavier Brenachot; Giorgio Ramadori; Rafael M. Ioris; Christelle Veyrat...; Jordi Altirriba; Ebru Aras; Sanda Ljubicic; Daisuke Kohno; Salvatore Fabbiano; Sophie Clement; Nicolas Goossens; Mirko Trajkovski; Sheila Harroch; Francesco Negro; Roberto Coppari
• Keywords: Adult; Blood Glucose; Lipopolysaccharides; Male; 0301 basic medicine; info:eu-repo/classification/ddc/616.07; Science; Gene Expression; ddc:616.07; Article; Cell Line; Mice; 03 medical and health sciences; info:eu-repo/classification/ddc/616; Animals; Humans; Insulin; info:eu-repo/classification/ddc/612; ddc:612; Aged; ddc:616; Inflammation; 2. Zero hunger; Interleukin-6; Gene Expression Profiling; Q; Hep G2 Cells; Lipid Metabolism; Diabetes Mellitus, Type 2; Liver; Female; Insulin Resistance

Abstract Obesity-induced inflammation engenders insulin resistance and type 2 diabetes mellitus (T2DM) but the inflammatory effectors linking obesity to are incompletely understood. Here, we show that hepatic expression of Protein Tyrosine Phosphatase Receptor Gamma (PTPR-γ) is stimulated by in obese/T2DM mice positively correlates with indices humans. NF-κB binds promoter Ptprg required for inflammation-induced PTPR-γ expression. loss-of-function lowers glycemia insulinemia enhancing insulin-stimulated suppression endogenous glucose production. These phenotypes rescued re-expression only liver lacking globally. Hepatic overexpression mimics levels found sufficient cause severe systemic resistance. We propose as a link between obesity-induced potential target treatment T2DM.