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

Xavier Brenachot, Giorgio Ramadori (), Rafael M. Ioris, Christelle Veyrat-Durebex, Jordi Altirriba, Ebru Aras, Sanda Ljubicic, Daisuke Kohno, Salvatore Fabbiano, Sophie Clement, Nicolas Goossens, Mirko Trajkovski, Sheila Harroch, Francesco Negro and Roberto Coppari ()
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Xavier Brenachot: Faculty of Medicine, University of Geneva
Giorgio Ramadori: Faculty of Medicine, University of Geneva
Rafael M. Ioris: Faculty of Medicine, University of Geneva
Christelle Veyrat-Durebex: Faculty of Medicine, University of Geneva
Jordi Altirriba: University of Geneva
Ebru Aras: Faculty of Medicine, University of Geneva
Sanda Ljubicic: Faculty of Medicine, University of Geneva
Daisuke Kohno: Gunma University
Salvatore Fabbiano: Faculty of Medicine, University of Geneva
Sophie Clement: Geneva University Hospitals, Rue Gabrielle Perret-Gentil
Nicolas Goossens: Geneva University Hospitals, Rue Gabrielle Perret-Gentil
Mirko Trajkovski: Faculty of Medicine, University of Geneva
Sheila Harroch: New York University Langone School of Medicine
Francesco Negro: University of Geneva
Roberto Coppari: Faculty of Medicine, University of Geneva

Nature Communications, 2017, vol. 8, issue 1, 1-9

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

Date: 2017
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02074-2

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DOI: 10.1038/s41467-017-02074-2

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