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

X Brenachot, G Ramadori, RM Ioris… - Nature …, 2017 - nature.com
X Brenachot, G Ramadori, RM Ioris, C Veyrat-Durebex, J Altirriba, E Aras, S Ljubicic…
Nature communications, 2017nature.com
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 …
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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