Evidence
Free Radic Biol Med. 2024 Apr 4:S0891-5849(24)00372-1. doi: 10.1016/j.freeradbiomed.2024.04.207. Online ahead of print.
ABSTRACT
BACKGROUND: Dysregulated ecto-nucleotide pyrophosphatase/phosphodiesterase (ENPP) family occurs in metabolic reprogramming pathological processes. Nonetheless, the epigenetic mechanisms by which ENPP family impacts NAFLD, also known as metabolic dysfunction-associated steatotic liver disease (MASLD), is poorly appreciated.
METHODS: We investigated the causes and consequences of ENPP1 promoter hypomethylation may boost NAFLD using NAFLD clinical samples, as well as revealed the underlying mechanisms using high-fat diet (HFD) + carbon tetrachloride (CCl4) induced mouse model of NAFLD and FFA treatment of cultured hepatocyte.
RESULTS: Herein, we report that the expression level of ENPP1 are increased in patients with NAFLD liver tissue and in mouse model of NAFLD. Hypomethylation of ENPP1, is associated with the perpetuation of hepatocyte autophagy and liver fibrosis in the NAFLD. ENPP1 hypomethylation is mediated by the DNA demethylase TET3 in NAFLD liver fibrosis and hepatocyte autophagy. Additionally, knockdown of TET3 methylated ENPP1 promoter, reduced the ENPP1 expression, ameliorated the experimental NAFLD. Mechanistically, TET3 epigenetically promoted ENPP1 expression via hypomethylation of the promoter. Knocking down TET3 can inhibit the hepatocyte autophagy but an overexpression of ENPP1 showing rescue effect.
CONCLUSIONS: We describe a novel epigenetic mechanism wherein TET3 promoted ENPP1 expression through promoter hypomethylation is a critical mediator of NAFLD. Our findings provide new insight into the development of preventative measures for NAFLD.
PMID:38582229 | DOI:10.1016/j.freeradbiomed.2024.04.207
Add to Google Keep
Post to X
Share on Linkedin
Estimated reading time: 4 minute(s)
Latest: Psychiatryai.com #RAISR4D
Cool Evidence: Engaging Young People and Students in Real-World Evidence ☀️
Real-Time Evidence Search [Psychiatry]
AI Research [Andisearch.com]
TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation
🌐 90 Days
VR Related Evidence Matrix
Evidence Blueprint
TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation
☊ AI-Driven Related Evidence Nodes
(recent articles with at least 5 words in title)
More Evidence
TET3 boosts hepatocyte autophagy and impairs non-alcoholic fatty liver disease by increasing ENPP1 promoter hypomethylation
🌐 365 Days
VR Related Evidence Matrix
