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Protein phosphatase 4 (PP4) functions as a critical regulator in tumor necrosis factor (TNF)-α-induced hepatic

Hongye Zhao1,2, Xiuqing Huang2, Juan Jiao1,2

  • 1Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Scientific Reports
|December 16, 2015
PubMed

Insights

Protein phosphatase 4 (PP4) plays a key role in hepatic insulin resistance by promoting the phosphorylation of IRS-1. Suppressing PP4 activity can ameliorate insulin resistance, highlighting its therapeutic potential.

Area of Science:

  • Biochemistry
  • Cellular Biology
  • Metabolic Research

Background:

  • Protein phosphatase 4 (PP4) is involved in DNA damage response, cell cycle, and embryo development.
  • Emerging evidence suggests PP4's role in glucose metabolism, but its function in hepatic insulin resistance is unclear.

Purpose of the Study:

  • To investigate the role of PP4 in tumor necrosis factor (TNF)-α-induced hepatic insulin resistance.

Main Methods:

  • Utilized db/db mice and TNF-α-treated C57BL/6J mice as in vivo models of hepatic insulin resistance.
  • Established in vitro models using HepG2 cells and primary hepatocytes treated with TNF-α.
  • Assessed PP4 expression, activity, and its interaction with IRS-1.

Main Results:

  • Increased PP4 expression and activity were observed in hepatic insulin resistance models (in vivo and in vitro).
  • PP4 silencing or activity suppression ameliorated TNF-α-induced insulin resistance.
  • PP4 overexpression exacerbated insulin resistance.
  • PP4 formed a complex with IRS-1, promoting IRS-1 serine 307 phosphorylation via JNK activation and reducing IRS-1 expression.

Conclusions:

  • PP4 is a significant regulator in inflammatory-related hepatic insulin resistance.
  • PP4's mechanism involves promoting IRS-1 phosphorylation and reducing its expression, contributing to insulin resistance.

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