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

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Author Brenachot Xavier, Ramadori Giorgio, Ioris Rafael M., Veyrat-Durebex Christelle, Altirriba Jordi, Aras Ebru, Ljubicic Sanda, Kohno Daisuke, Fabbiano Salvatore, Clement Sophie, Goossens Nicolas, Trajkovski Mirko, Harroch Sheila, Negro Francesco, Coppari Roberto,
Project Metabolic homeostasis through physiological stimulation of beige fat development
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Original article (peer-reviewed)

Journal Nature Communications
Volume (Issue) 8(1)
Page(s) 1820 - 1820
Title of proceedings Nature Communications
DOI 10.1038/s41467-017-02074-2

Open Access

URL https://www.ncbi.nlm.nih.gov/pubmed/29180649
Type of Open Access Website

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.
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