Green Tea Polyphenol Epigallocatechin-3-Gallate Enhance Glycogen Synthesis and Inhibit Lipogenesis in Hepatocytes

Abstract

The beneficial effects of green tea polyphenols (GTP) against metabolic syndrome and type 2 diabetes by suppressing appetite and nutrient absorption have been well reported. However the direct effects and mechanisms of GTP on glucose and lipid metabolism remain to be elucidated. Since the liver is an important organ involved in glucose and lipid metabolism, we examined the effects and mechanisms of GTP on glycogen synthesis and lipogenesis in HepG2 cells. Concentrations of GTP containing 68% naturally occurring (−)-epigallocatechin-3-gallate (EGCG) were incubated in HepG2 cells with high glucose (30 mM) under 100 nM of insulin stimulation for 24 h. GTP enhanced glycogen synthesis in a dose-dependent manner. 10 μM of EGCG significantly increased glycogen synthesis by 2fold (P < 0.05) compared with insulin alone. Western blotting revealed that phosphorylation of Ser9 glycogen synthase kinase 3β and Ser641 glycogen synthase was significantly increased in GTP-treated HepG2 cells compared with nontreated cells. 10 μM of EGCG also significantly inhibited lipogenesis (P < 0.01). We further demonstrated that this mechanism involves enhanced expression of phosphorylated AMP-activated protein kinase α and acetyl-CoA carboxylase in HepG2 cells. Our results showed that GTP is capable of enhancing insulin-mediated glucose and lipid metabolism by regulating enzymes involved in glycogen synthesis and lipogenesis.

Potential Biological Effects of (‐)‐Epigallocatechin‐3‐gallate on the Treatment of Nonalcoholic Fatty Liver Disease

“…In a study that investigated inhibitory effect of EGCG on FFA‐induced lipid accumulation, HepG2 cells were exposed to FFA co‐treated with 50 μM EGCG, and the final results, which were analyzed by proteomic analysis, demonstrated that EGCG reduced cellular lipid accumulation through the activation of AMPK and then shifted some FFA toward oxidation and away from lipid and triglyceride storage. A similar report showed that 10 μM EGCG inhibited hepatic lipogenesis by 65% ( p <0.01) by increasing expressions of phospho‐AMPKα (Thr172) and phospho‐ACC (Ser79) in high‐glucose‐treated HepG2 cells . These studies suggest that EGCG is a potent activator of the AMPK pathway.…”

Japanese quince (Chaenomeles japonica L.) fruit polyphenolic extract modulates carbohydrate metabolism in HepG2 cells via AMP-activated protein kinase

“…We suggest that this effects caused by the JQ were partly AMPK-dependent, because HepG2 cells pretreatment with compound C abolished the JQ ability to inhibit gluconeogenesis and stimulate glucose uptake under normal glucose level (Figure 4), but this hypothesis needs further studies. The JQ polyphenols were also able to increase glycogen synthesis and that finding is consistent with the results obtained for HepG2 cells treated under hyperglycemic conditions with EGCG and green tea polyphenols (Kim et al, 2013).…”

Adaptive Cellular Stress Pathways as Therapeutic Targets of Dietary Phytochemicals: Focus on the Nervous System

“…Several phytochemicals can inhibit GSK-3b activity (Table 8). The beneficial effects of EGCG against the metabolic syndrome are mediated, in part, by GSK-3b inhibition, which enhances insulin sensitivity and activates enzymes involved in glycogen synthesis and lipogenesis (Kim et al, 2013b). Administration of green tea polyphenols decreases GSK-3b and the detrimental effects of a high-fructose diet on insulin signaling, lipid metabolism, and inflammation in the cardiac muscle of rats (Qin et al, 2010).…”