Hepatic protein tyrosine phosphatase receptor gamma links obesity-induced inflammation to insulin resistance.
Xavier BrenachotGiorgio RamadoriRafael M IorisChristelle Veyrat-DurebexJordi AltirribaEbru ArasSanda LjubicicDaisuke KohnoSalvatore FabbianoSophie ClementNicolas GoossensMirko TrajkovskiSheila HarrochFrancesco NegroRoberto CoppariPublished in: Nature communications (2017)
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.
Keyphrases
- insulin resistance
- high fat diet induced
- oxidative stress
- metabolic syndrome
- adipose tissue
- type diabetes
- diabetic rats
- glycemic control
- high fat diet
- skeletal muscle
- polycystic ovary syndrome
- high glucose
- poor prognosis
- weight loss
- drug induced
- binding protein
- cardiovascular disease
- gene expression
- cell proliferation
- blood glucose
- body mass index
- dna methylation
- climate change
- endothelial cells
- protein kinase
- combination therapy
- cardiovascular risk factors
- long non coding rna