Effects of AhR-activating PAHs on glucose transport and metabolism in liver cells

PETRÁŠ, Jiří, Anna LNĚNIČKOVÁ, Miroslav MACHALA and Jan VONDRÁČEK. Effects of AhR-activating PAHs on glucose transport and metabolism in liver cells. In Květinův Den 2024. 2024. ISBN 978-80-11-04935-5.

Basic information

• Original name: Effects of AhR-activating PAHs on glucose transport and metabolism in liver cells
• Authors: PETRÁŠ, Jiří, Anna LNĚNIČKOVÁ, Miroslav MACHALA and Jan VONDRÁČEK.
• Edition: Květinův Den 2024, 2024.

Other information

• Original language: English
• Type of outcome: Presentations at conferences
• Field of Study: 10511 Environmental sciences
• Confidentiality degree: is not subject to a state or trade secret
• WWW: URL
• Organization unit: Faculty of Science
• ISBN: 978-80-11-04935-5
• Keywords in English: Aryl Hydrocarbon Receptor, Glucose Metabolism, Hepatocytes, Pollutants

Abstract

Polyaromatic hydrocarbons (PAHs) are a large group of environmental pollutants. They can be found in the aquatic environment, in the soil, or as a significant part of airborne particulate pollution. PAHs often exhibit carcinogenic, genotoxic and endocrine-disrupting effects. Recently, other effects of these hazardous substances have become gradually revealed, for example, the disruption of immune processes or cellular energy metabolism, which is of a primary concern. The effects of PAHs are often mediated via activation of the aryl hydrocarbon receptor (AhR). A well-known representative of these substances is benzo(k)fluoranthene (BkF), a common air pollutant associated with particulate matter and a potent activator of AhR. When AhR is activated, it subsequently translocated into the nucleus where it functions as a transcription factor for specific genes, such as those encoding cytochrome P450 family 1 enzymes, which metabolize potentially harmful xenobiotics, and may produce a wide range of bioactive PAH metabolites. Here, we used cell lines derived from human liver (HepaRG, HepG2 and MIHA), focusing on glucose transport/metabolism that can be impacted by PAHs. Treatment of liver cells with strong AhR agonists resulted in suppression of the expression of genes associated with carbohydrate metabolism. These genes included e.g. PCK1 (enzyme acting as a major control point of gluconeogenesis), GLUT2 (a major glucose transporter in liver cells) and GLUT9 (a transporter of uric acid, glucose and fructose). Other glucose transporters were also potentially affected. In addition, analysis of cell culture medium also confirmed that production/transport of glucose in cells that were cultivated in glucose-free medium is also impaired. Our results suggest that AhR activation in liver cell models suppressed the expression of genes associated with carbohydrate metabolism, including several glucose transporters. As a result, the transport of glucose from the cytoplasm was also significantly reduced. This suggests a need to focus on potential relationship between some PAHs and development of metabolic disorders in the liver tissue. [Supported by the project No. 24-10086S of the Czech Science Foundation].