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Updated: Nov 15, 2025

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis
08:58

Optimized Analysis of In Vivo and In Vitro Hepatic Steatosis

Published on: March 11, 2017

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WW domain-binding protein 2 overexpression prevents diet-induced liver steatosis and insulin resistance through

Zhe Zheng1,2, Yue Li1,2, Siyuan Fan1,2

  • 1Clinic Center of Human Gene Research, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cell Death & Disease
|March 4, 2021
PubMed

Insights

Transcriptional coactivator WW domain-binding protein 2 (WBP2) protects against nonalcoholic fatty liver disease (NAFLD). WBP2 overexpression alleviates fat deposition and insulin resistance, offering a new therapeutic target for NAFLD.

Area of Science:

  • Hepatology
  • Molecular Biology
  • Oncology

Background:

  • Nonalcoholic fatty liver disease (NAFLD) is a widespread condition with unclear pathological mechanisms and no approved treatments.
  • Transcriptional coactivator WW domain-binding protein 2 (WBP2), an oncogene involved in breast cancer, has shown decreased expression in NAFLD patients.

Purpose of the Study:

  • To investigate the role of WBP2 in the pathogenesis of NAFLD.
  • To explore WBP2 as a potential therapeutic target for NAFLD.

Main Methods:

  • Adeno-associated virus (AAV)-mediated in vivo overexpression and knockdown of WBP2 in mouse models of high-fat diet (HFD)-induced NAFLD.
  • In vitro studies using human hepatocyte cell line (LO2) and primary mouse hepatocytes with palmitic acid (PA) treatment.
  • Mass spectrometry to identify WBP2 interacting proteins.
  • Site-directed mutagenesis to investigate WBP2-AMPKβ1 interaction and phosphorylation.

Main Results:

  • In vivo WBP2 overexpression alleviated HFD-induced liver fat deposition and insulin resistance, while WBP2 knockdown aggravated these conditions.
  • In vitro, WBP2 overexpression reduced PA-induced fat accumulation in hepatocytes, whereas WBP2 knockout/knockdown exacerbated it.
  • Mass spectrometry identified AMPKβ1 as a WBP2-binding protein.
  • WBP2 induces phosphorylation of AMPKβ1 at S108, activating the AMPK pathway and influencing lipid metabolism.

Conclusions:

  • WBP2 plays a protective role in NAFLD by regulating lipid metabolism through the AMPK pathway.
  • WBP2 represents a promising novel therapeutic target for the treatment of NAFLD.

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