The methyltransferase METTL3-mediated fatty acid metabolism revealed the mechanism of cinnamaldehyde on alleviating steatosis

As a primarily N6-methyladenosine methyltransferase, methyltransferase 3 (METTL3) plays a crucial role in nonalcoholic fatty liver disease. However, its regulatory mechanism in steatosis remains unknown. Alpha mouse liver 12 (AML12) cells were induced by free fatty acids (FFA). Triglycerides, lipid...

Full description

Saved in:
Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2022-09, Vol.153, p.113367-113367, Article 113367
Main Authors: Xu, Ruohui, Xiao, Xiaoli, Zhang, Shengan, Pan, Jiashu, Tang, Yingjue, Zhou, Wenjun, Ji, Guang, Dang, Yanqi
Format: Article
Language:English
Subjects:
Cinnamaldehyde
Fatty acids metabolism
METTL3
Steatosis
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:As a primarily N6-methyladenosine methyltransferase, methyltransferase 3 (METTL3) plays a crucial role in nonalcoholic fatty liver disease. However, its regulatory mechanism in steatosis remains unknown. Alpha mouse liver 12 (AML12) cells were induced by free fatty acids (FFA). Triglycerides, lipid droplet assay, and Oil Red O staining were performed to evaluate steatosis. The expression of METTL3 and cytochrome P450 family 4 subfamily f polypeptide 40 (CYP4F40) was measured using Western blotting, real-time quantitative polymerase chain reaction, and dual-luciferase reporter assay. Triglycerides, total cholesterol, almandine aminotransferase, and aspartate aminotransferase were assayed after cinnamaldehyde treatment. Transcriptomics and metabolomics were performed to determine how METTL3 and cinnamaldehyde regulate steatosis. METTL3 protein level was reduced in FFA-induced steatosis in AML12 cells, and METTL3 knockdown aggravated the steatosis. Cinnamaldehyde alleviated steatosis by increasing METTL3 expression. A combined transcriptomics and metabolomics analysis revealed that METTL3 knockdown reduced CYP4F40 expression and reduced the level of capric acid, gamma-linolenic acid, arachidonic acid, and docosapentaenoic acid. Cinnamaldehyde promoted CYP4F40 expression by increasing METTL3 and increased the levels of capric acid, gamma-linolenic acid, arachidonic acid, and docosapentaenoic acid. Finally, the beneficial effects of cinnamaldehyde on steatosis were reversed after METTL3 knockdown. METTL3 knockdown aggravated steatosis in AML12 cells through CYP4F40-mediated fatty acid metabolism, and cinnamaldehyde alleviated steatosis via the METTL3-CYP4F40 pathway. [Display omitted]
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2022.113367