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EZH2-Mediated H3K27 Trimethylation in the Liver of Mice Is an Early Epigenetic Event Induced by High-Fat Diet Exposure.

Authors :
Pinton, Giulia
Perucca, Mattia
Gigliotti, Valentina
Mantovani, Elena
Clemente, Nausicaa
Malecka, Justyna
Chrostek, Gabriela
Dematteis, Giulia
Lim, Dmitry
Moro, Laura
Chiazza, Fausto
Source :
Nutrients; Oct2024, Vol. 16 Issue 19, p3260, 12p
Publication Year :
2024

Abstract

Background/Objectives: Methyltransferase EZH2-mediated H3K27me3 is involved in liver inflammation and fibrosis, but its role in hepatic metabolic derangements is not yet clearly defined. We investigated if a high-fat diet (HFD) induced early changes in EZH2 expression and H3K27 me3 in the liver of mice. Methods: Five-week-old mice were fed an HFD or a low-fat diet (Control) for 2 weeks (2 W) or 8 weeks (8 W). Body weight was recorded weekly. Glycemia and oral glucose tolerance were assessed at baseline and after 2 W–8 W. Finally, livers were collected for further analysis. Results: As expected, mice that received 8 W HFD showed an increase in body weight, glycemia, and liver steatosis and an impairment in glucose tolerance; no alterations were observed in 2 W HFD mice. Eight weeks of HFD caused hepatic EZH2 nuclear localization and increased H3 K27me3; surprisingly, the same alterations occurred in 2 W HFD mice livers, even before overweight onset. We demonstrated that selective EZH2 inhibition reduced H3K27me3 and counteracted lipid accumulation in HUH-7 cells upon palmitic acid treatment. Conclusions: In conclusion, we point to EZH2/H3K27me3 as an early epigenetic event occurring in fatty-acid-challenged livers both in vivo and in vitro, thus establishing EZH2 as a potential pharmacological target for metabolic derangements. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
20726643
Volume :
16
Issue :
19
Database :
Complementary Index
Journal :
Nutrients
Publication Type :
Academic Journal
Accession number :
180275473
Full Text :
https://doi.org/10.3390/nu16193260