Epigallocatechin-3-gallate (EGCG) has been shown to attenuate obesity, fatty liver disease, hepatic inflammation and lipid profiles. Here, we validate the efficacy of EGCG in a murine model of non-alcoholic fatty liver disease (NAFLD) and extend the mechanistic insights. NAFLD was induced in mice by a high-fat diet (HFD) with 30% fructose. EGCG was administered at a low dose (25 mg/kg/day, EGCG-25) or high dose (50 mg/kg/day, EGCG-50) for 8 weeks. In HFD-fed mice, EGCG attenuated body and liver weight by ~22% and 47%, respectively, accompanied by ~47% reduction in hepatic triglyceride (TG) accumulation and ~38% reduction in serum cholesterol, resonating well with previous reports in the literature. In EGCG-treated mice, the hepatic steatosis score and the non-alcoholic steatohepatitis activity score were both reduced by ~50% and ~57%, respectively, accompanied by improvements in hepatic inflammation grade. Liver enzymes were improved ~2–3-fold following EGCG treatment, recapitulating previous reports. Hepatic flow cytometry demonstrated that EGCG-fed mice had lower Ly6C+, MHCII+ and higher CD206+, CD23+ hepatic macrophage infiltration, indicating that EGCG impactedM1/M2 macrophage polarization. Our study further validates the salubrious effects of EGCG on NAFLD and sheds light on a novel mechanistic contribution of EGCG, namely hepatic M1-to-M2 macrophage polarization. These findings offer further support for the use of EGCG in human NAFLD.

Epigallocatechin-3-gallate (EGCG) is a polyphenol green tea catechin with potential health benefits and therapeutic effects in non-alcoholic fatty liver disease (NAFLD), a common liver disorder that adversely affects liver function and lipid metabolism. This systematic review surveyed the effects of EGCG or green tea extract (GTE) on NAFLD reported in studies involving rodent models or humans with a focus on clinicopathologic outcomes, lipid and carbohydrate metabolism, and inflammatory, oxidative stress, and liver injury markers. Articles involving clinical efficacy of EGCG/GTE on human subjects and rodent models were gathered by searching the PUBMED database and by referencing additional articles identified from other literature reviews. EGCG or GTE supplementation reduced body weight, adipose tissue deposits, and food intake. Mechanistically, the majority of these studies confirmed that EGCG or GTE supplementation plays a significant role in regulating lipid and glucose metabolism and expression of genes involved in lipid synthesis. Importantly, EGCG and GTE supplementation were shown to have beneficial effects on oxidative stress-related pathways that activate pro-inflammatory responses, leading to liver damage. In conclusion, green tea catechins are a potentially useful treatment option for NAFLD. More research is required to determine the ideal dosage, treatment duration, and most effective delivery method of EGCG or GTE, and to provide more definitive conclusions by performing large, randomized clinical trials.