High Fat Diet and Ethanol-Induced Fatty Liver Disease Mouse Model

Abstract

A diet high in fat and/or alcohol is a major cause of fatty liver disease (FLD), which is a common precursor to chronic liver disease. As the pathogenetic mechanisms of FLD remain unclear, an appropriate animal model is critical to problem solving in this field. This study aimed to develop an FLD mouse model using a diet high in fat and/or ethanol. Five-week-old female ICR mice were given free access to a high fat diet (HFD, 60 kcal % fat of total food), or daily intragastrically administered ethanol (E, 0.5 g/kg/day), or a combination of HFD and ethanol (HFD+E). Hepatic histology was observed with oil red O (ORO) staining. Hepatic triglyceride (TG) levels, antioxidant enzyme activities, and mRNA expression levels of metabolic, antioxidant, and inflammatory genes, i.e. peroxisome proliferator activated receptor-alpha and gamma (Ppar-α and Ppar-γ), sterol regulatory element binding protein-1 (Srebp-1), acetyl-CoA carboxylase (Acc), fatty acid synthase (Fas), fat cluster of differentiation (Cd-36), catalase (Cat), superoxide dismutase 1 and 2 (Sod1 and Sod2), glutathione peroxidase (Gpx), nuclear factor-kappa b (Nf-ĸb), tumor necrosis factor-alpha (Tnf-α), and monocyte chemoattractant protein-1 (Mcp-1) were determined. HFD+E induced FLD in mice by increasing hepatic TG levels and expression of Acc and Fas metabolic genes and Cd-36 and Mcp-1 inflammatory genes, while simultaneously reducing the activity and expression of antioxidant enzymes. These findings confirm that HFD+E is a potent regimen for FLD induction in mice. Keywords: High fat diet, Alcohol, Non-invasive, Antioxidation, Metabolic gene, Inflammatory gene

A review of edible plant-derived natural compounds for the therapy of liver fibrosis

“…Furthermore, hesperidin mitigates ConA or alpha-naphthylisothiocyanate (ANIT)induced mouse liver damage through inhibiting oxidative stress, inflammation, HMGB1 expression and T-cell activation, and promoting farnesoid X receptor (FXR) activation [177,178]. Furthermore, in HFD or HFD + alcohol-induced rodent model, hesperidin alleviates liver damage by reducing oxidative stress and endoplasmic reticulum stress-induced inflammation, and activating AMPK pathway [179][180][181].…”