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The Role of PPAR‐g in Shp1‐Mediated Regulation of Glucose Homeostasis in the Liver
Author(s) -
Gomez Lilian,
LavalléeBourget MarieHélène,
Forest MariePier,
Schwab Michael,
Bellmann Kerstin,
SolaPenna Mauro,
Deshaies Yves,
Marette André
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1014.12
Subject(s) - medicine , endocrinology , rosiglitazone , insulin resistance , steatosis , glucose homeostasis , glucokinase , insulin , insulin tolerance test , inflammation , protein kinase b , glucose tolerance test , chemistry , phosphorylation , biochemistry , insulin sensitivity
The protein‐tyrosine phosphatase Shp1 plays a central role in high‐fat diet (HFD)‐induced insulin resistance. This enzyme, which negatively regulates insulin action on glucose homeostasis, is upregulated in metabolic tissues, such as liver, muscle and adipose tissue, of mice submitted to HFD. Hepatocyte‐specific Shp1 knockout mice (Ptpn6 H‐KO ) submitted to HFD develop hepatic steatosis but show less hepatic insulin resistance. These effects might be due to the observed attenuation of HFD‐induced inflammation and liver damage. Moreover, while Ptpn6 H‐KO mice present a significant increase in PPARg expression, overexpression of Shp1 reduces the activity of this nuclear receptor. The aim of the present study is to evaluate the role of PPARg on the amelioration of liver inflammation in HFD‐fed Ptpn6 H‐KO mice. For this, male Ptpn6 H‐KO mice were kept on standard diet (SD) or HFD for 18 weeks. During the last 4 weeks the animals were treated with a very low dose of rosiglitazone, a known PPARg agonist. Rosiglitazone‐treated Ptpn6 H‐KO mice showed an improvement in glucose tolerance without a significant change in insulinemia during oral glucose tolerance test. Insulin‐induced Akt phosphorylation, was increased by rosiglitazone in the Ptpn6 H‐KO mice, which may partially explain the amelioration in glucose tolerance. Despite the fact that rosiglitazone increased hepatic steatosis in Ptpn6 H‐KO mice, the drug also augmented the levels of the anti‐inflammatory cytokine, IL‐10. However, rosiglitazone did not improve the pattern of pro‐inflammatory cytokines in the liver. Altogether, our data support that Shp1 effects on glucose homeostasis involve the activation of PPARg, but the complete role of these players on liver inflammation has yet to be elucidated. Support or Funding Information Canadian Institutes of Health Research and CNPq