Loading
Life sciences · Journal article
Advanced Science · October 11, 2026
No summary has been generated for this record yet. What follows is drawn from its source metadata only.
Journal article.
No findings were extractable from the material analysed.
Safety was not reported in the material analysed. Check the source before drawing any conclusion about harm.
The source did not state who this applies to in practice.
Graded across the dimensions that decide whether you should act, each from what the source actually supports. There is no single score, and where a dimension was not assessed it says so.
This record has not been graded across any dimension yet. Treat the label above as provisional and read the source.
What is missing. This record has no bottom line, key findings, reported figures, evidence dimensions. That is a gap in the analysis, not a judgement about the study.
ABSTRACT Metabolic dysfunction‐associated steatohepatitis (MASH) is driven by nutrient stress through incompletely defined epigenetic mechanisms. This study demonstrates that lipid stress activates the hexosamine biosynthesis pathway (HBP), elevating O ‐linked β‐N‐acetylglucosamine ( O ‐GlcNAc) modification of the N6‐methyladenosine (m6A) demethylase fat mass and obesity‐associated protein (FTO) at Ser195. This post‐translational modification recruits the deubiquitinase ubiquitin‐specific peptidase 20 (USP20), displaces the E3 ligase F‐box and WD repeat domain containing 7 (FBXW7), and enhances FTO protein stability and m6A demethylase activity. O ‐GlcNAc‐dependent FTO activation removes m6A from Harvey rat sarcoma viral oncogene homolog ( HRAS ) mRNA, evades YTH N6‑methyladenosine RNA binding protein 2 (YTHDF2)‑mediated degradation, and prolongs transcript half‐life. Subsequent HRAS upregulation activates the PI3K/AKT signaling pathway, driving hepatic steatosis and inflammation. Administration of a novel cell‐penetrating peptide (CPP) designed to block FTO O ‐GlcNAcylation at Ser195 effectively ameliorates MASH progression in vitro and in vivo. These findings establish FTO O ‐GlcNAcylation as a druggable metabolic‐epigenetic checkpoint in MASH pathogenesis, revealing a promising therapeutic strategy for this increasingly prevalent liver disease.