Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, stimulates hepatic autophagy and lipid clearance

PLoS One. 2014 Jan 29;9(1):e87161. doi: 10.1371/journal.pone.0087161. eCollection 2014.

Abstract

Epigallocatechin gallate (EGCG) is a major polyphenol in green tea that has been shown to have anti-inflammatory, anti-cancer, anti-steatotic effects on the liver. Autophagy also mediates similar effects; however, it is not currently known whether EGCG can regulate hepatic autophagy. Here, we show that EGCG increases hepatic autophagy by promoting the formation of autophagosomes, increasing lysosomal acidification, and stimulating autophagic flux in hepatic cells and in vivo. EGCG also increases phosphorylation of AMPK, one of the major regulators of autophagy. Importantly, siRNA knockdown of AMPK abrogated autophagy induced by EGCG. Interestingly, we observed lipid droplet within autophagosomes and autolysosomes and increased lipid clearance by EGCG, suggesting it promotes lipid metabolism by increasing autophagy. In mice fed with high-fat/western style diet (HFW; 60% energy as fat, reduced levels of calcium, vitamin D3, choline, folate, and fiber), EGCG treatment reduces hepatosteatosis and concomitantly increases autophagy. In summary, we have used genetic and pharmacological approaches to demonstrate EGCG induction of hepatic autophagy, and this may contribute to its beneficial effects in reducing hepatosteatosis and potentially some other pathological liver conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylate Kinase / metabolism
  • Animals
  • Autophagy*
  • Catechin / analogs & derivatives*
  • Catechin / pharmacology
  • Diet, High-Fat
  • Fatty Liver / drug therapy
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Hep G2 Cells
  • Hepatocytes / drug effects
  • Hepatocytes / physiology
  • Humans
  • Lipid Metabolism / drug effects*
  • Liver / drug effects
  • Liver / metabolism
  • Liver / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Phagosomes / metabolism
  • Tea / chemistry

Substances

  • Tea
  • Catechin
  • epigallocatechin gallate
  • Adenylate Kinase

Grant support

This work was supported by Duke-NUS Graduate Medical School Faculty Funds (PMY) sponsored by the Ministry of Health, Ministry of Education, and Ministry of Trade, Singapore and A*StaR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuript.