By studying several knockout models, the researchers discovered that more severe diet-induced NASH resulted from influx of intestinally derived toll-like receptor 4 (TLR4) and toll-like receptor 9 (TLR9) agonists into the portal circulation, which, in turn, activated tumor necrosis factor alpha (TNFα) in the liver. Here, TLR4 is linked to metabolic dysfunction-associated steatohepatitis.