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Impact of perinatal exposure to acetaminophen on hepatocellular metabolic function in offspring

Ka Wu1, Chao Guo2, Xiuli Lu2

  • 1Department of Pharmacy, The Second People's Hospital of Nanning City, The Third Affiliated Hospital of Guangxi Medical University Nanning 530031, Guangxi, PR China.

American Journal of Translational Research
|January 13, 2017
PubMed

Insights

Perinatal acetaminophen (APAP) exposure in mice disrupts offspring glucose metabolism. This may be linked to impaired insulin signaling and reduced glucose transporter levels in the liver.

Area of Science:

  • Toxicology
  • Developmental Biology
  • Metabolic Disorders

Background:

  • Acetaminophen (APAP) is a common over-the-counter antipyretic, with known dose-dependent cytotoxicity.
  • The impact of prenatal acetaminophen exposure on offspring metabolic function is largely uninvestigated.

Purpose of the Study:

  • To investigate the potential adverse effects of perinatal acetaminophen exposure on liver metabolic function in offspring.
  • To assess the impact on glucose metabolism and insulin signaling pathways.

Main Methods:

  • Established a mouse model of prenatal acetaminophen exposure.
  • Analyzed metabolic parameters (glucose, insulin, glycogen) in postnatal offspring.
  • Utilized immunoblotting to assess protein expression (insulin receptor, IRS1, Akt, GSK-3β).
  • Determined hepatic glucose transporter 2 (GLUT2) levels via immunohistochemistry.

Main Results:

  • Acetaminophen-exposed offspring exhibited impaired glucose metabolism, elevated plasma insulin, and reduced liver glycogen.
  • Decreased expression of IRS1, phospho-GSK-3β, and phospho-Akt proteins was observed.
  • Down-regulation of hepatic glucose transporter 2 (GLUT2) was evident in exposed offspring.

Conclusions:

  • Perinatal acetaminophen exposure impairs hepatic glucose metabolism in offspring.
  • This impairment may be associated with disruptions in insulin-dependent AKT signaling.
  • Findings suggest potential risks of prenatal acetaminophen exposure on metabolic health.

Keywords:
Acetaminophenglucose metabolismliverperinatal exposure

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