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The Putative Antilipogenic Role of NRG4 and ERBB4: First Expression Study on Human Liver Samples

Maria Bograya1, Maria Vulf1, Anastasia Minchenko1

  • 1Center for Immunology and Cellular Biotechnology, Institute of Medicine and Life Sciences, Immanuel Kant Baltic Federal University, 236001 Kaliningrad, Russia.

Frontiers in Bioscience (Landmark Edition)
|December 30, 2024
PubMed
Abstract

Insights

In individuals with obesity, lower levels of epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) mRNA were observed. These findings suggest a potential role in hepatic lipid metabolism, distinct from non-alcoholic fatty liver disease (NAFLD).

Area of Science:

  • Metabolic research
  • Hepatology
  • Molecular biology

Background:

  • Epidermal growth factor receptor 4 (ERBB4) and neuregulin 4 (NRG4) show promise in reducing steatosis in mouse models.
  • Their role in human non-alcoholic fatty liver disease (NAFLD) remains largely unexplored.
  • This study investigates ERBB4 and NRG4 in humans with obesity, type 2 diabetes, and NAFLD.

Purpose of the Study:

  • To investigate the expression of ERBB4 and NRG4 mRNAs in human liver.
  • To assess the role of ERBB4 and NRG4 in lipid metabolism in individuals with obesity and NAFLD.
  • To explore the relationship between ERBB4, NRG4, and NAFLD progression.

Main Methods:

  • Obtained liver biospecimens from 80 individuals undergoing surgery.
  • Quantified ERBB4, NRG4, and lipogenesis gene mRNA expression using RT-qPCR.
  • Performed histological analysis on 36 biopsies and correlated transcript levels with NAFLD stage.

Main Results:

  • Individuals with elevated BMI showed decreased ERBB4 and NRG4 mRNA levels.
  • Increased acetyl-CoA carboxylase alpha (ACACA) mRNA levels were observed in individuals with elevated BMI.
  • A significant negative correlation was found between NRG4 and ACACA mRNA levels, but no deregulation was seen in NAFLD patients.

Conclusions:

  • ERBB4 and NRG4 mRNA expression decreases in the livers of individuals with high BMI, but not in those with NAFLD.
  • Assessed correlations between ERBB4, NRG4, and key lipogenesis genes.
  • Hypothesized a model for NRG4-mediated suppression of hepatic de novo lipogenesis, opening new research avenues.
Keywords:
ERBB4NAFLDNASHNRG4obesitysteatosis

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