Core Concepts
Pharmacological activation of FXR by hammerhead-type agonists induces a novel liver-specific enhancer-derived lncRNA, FincoR, contributing to the amelioration of NASH in mice.
Abstract
The study explores how FXR activation affects the expression of long non-coding RNAs (lncRNAs) through the discovery of a liver-enriched enhancer-derived lncRNA named FincoR. The research demonstrates that FincoR is specifically induced by hammerhead-type FXR agonists and plays a crucial role in reducing liver fibrosis and inflammation in NASH treatment. The findings highlight the potential of FincoR as a new drug target for metabolic disorders, including NASH.
Stats
GW4064 treatment induced over 10-fold expression of FincoR in mouse liver.
190 high-confidence eRNAs were identified in mouse liver, with 14 upregulated and 5 downregulated by GW4064 treatment.
Short-time GW4064 treatment resulted in 590 up-regulated genes and 500 down-regulated genes.
ChIP assays confirmed increased recruitment of FXR, RXR𝛂, and BRD4 to the enhancer region close to the transcription start site of FincoR after GW4064 treatment.
Quotes
"FincoR is specifically induced by hammerhead-type FXR agonists, contributing to the amelioration of NASH."
"CRISPR/Cas9-mediated knockdown of FincoR reduced beneficial effects of tropifexor on liver fibrosis and inflammation."
"Tropifexor-mediated reduction in hepatic steatosis was independent of FincoR expression."