With the aim of generating a mouse model of alcoholic liver disease that would rapidly develop steatosis, inflammation as well as fibrosis, we formulated a regimen that combined chronic injections of low dose (2mg/kg) lipopolysaccharide (LPS) with Lieber DeCarli-based diet containing 6.7% ethanol feeding to mice with impaired TGF-β signaling through constitutive disruption of β2-spectrin and/or Smad3. Here, SMAD3 is linked to steatosis.