A glycoprotein linking diet, microbiota, and gut-liver dysfunction identified!
The mechanisms linking gut barrier dysfunction to early progression of metabolic dysfunction-associated steatotic liver disease (MASLD) is poorly understood.
The researchers in this study identify intestinal angiopoietin-like 4 (Angptl4) as a central integrator of dietary and microbial signals that governs barrier integrity and hepatic oxidative stress, key early MASLD features.
They demonstrate that intestinal Angptl4 expression is regulated by dietary fatty acids via PPARα signaling and microbiota-derived pattern-recognition pathways, including flagellin-activated-TLR5-EGR1 activation, alongside diet-associated shifts in TLR signaling. These signals destabilize epithelial barriers, amplifying gut-to-liver metabolic and microbial flux.
The authors also observed increase in fecal Angptl4 n human cohorts with dysbiosis and metabolic dysfunction.
