3rd Edition of Diabetes and Endocrinology World Conference 2027

Abstract

Abstract: 
Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the most common liver diseases globally. It can progress to severe conditions such as non-alcoholic steatohepatitis, liver cirrhosis, and hepatocellular carcinoma. Recent studies have shown that translational regulation is a key mechanism in the progression of MASLD, and N6-methyladenosine (m6A) RNA methylation plays an important role in this process. Betaine, a natural methyl donor, has been proven to significantly improve fatty liver. However, it is unclear whether betaine improves MASLD through m6A-regulated translation.
This study explored betaine’s effect on high-fat-diet-induced mouse hepatic steatosis and its regulatory mechanism of translation via m6A methylation, combining animal/cell experiments with multi-omics (m6A-seq, RNC-seq, RNA-seq) analysis.

Results showed that betaine significantly improves hepatic lipid accumulation and reduces hepatocyte injury. m6A-seq reveals significant differences in m6A-modified genes between the high-fat diet (HFD) and high-fat diet with betaine (HBD) groups, with these genes enriched in lipid metabolism pathways. The translation rate (TR) of transcripts with m6A modification is significantly increased, and there is a positive correlation between m6A modification levels and translation efficiency, particularly with CDS region modification playing a crucial role. Through PPI network analysis, ANKHD1 is identified as a key gene in betaine's m6A modification regulation of hepatic steatosis. In vitro experiments confirm the abnormal expression of ANKHD1 at the translational level and show that betaine reduces lipid accumulation by enhancing ANKHD1’s translation efficiency.

This study comprehensively maps the impact of m6A methylation in betaine's improvement of hepatic steatosis. Betaine reduces liver fat accumulation by modulating m6A methylation to enhance mRNA translation. Additionally, ANKHD1 is found to be a novel potential therapeutic target gene for MASLD.