Epigallocatechin-3-gallate (EGCG), a green tea polyphenol, stimulates hepatic autophagy and lipid clearance.
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.
Program of Cardiovaular and Metabolic Disorders, Duke-NUS Graduate Medical hool, Singapore, Singapore.
Jin
J
Zhou
Program of Cardiovaular and Metabolic Disorders, Duke-NUS Graduate Medical hool, Singapore, Singapore.
Benjamin Livingston
BL
Farah
Program of Cardiovaular and Metabolic Disorders, Duke-NUS Graduate Medical hool, Singapore, Singapore.
Rohit Anthony
RA
Sinha
Department of Anatomy, Yong Loo Lin hool of Medicine, National University of Singapore, Singapore, Singapore.
Yajun
Y
Wu
Program of Cardiovaular and Metabolic Disorders, Duke-NUS Graduate Medical hool, Singapore, Singapore.
Brijesh Kumar
BK
Singh
Department of Anatomy, Yong Loo Lin hool of Medicine, National University of Singapore, Singapore, Singapore.
Boon-Huat
BH
Bay
Departments of Chemical Biology, Ernest Mario hool of Pharmacy, Rutgers, The State University of New Jersey, Piataway, New Jersey, United States of America.
Chung S
CS
Yang
Program of Cardiovaular and Metabolic Disorders, Duke-NUS Graduate Medical hool, Singapore, Singapore ; Sarah W. Stedman Nutrition and Metabolism Center, Departments of Medicine and Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina, United States of America.
Paul Michael
PM
Yen
D000263:Adenylate Kinase / Q000378:metabolism; D000818:Animals; D001343:Autophagy; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D059305:Diet, High-Fat; D005234:Fatty Liver / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism; D056945:Hep G2 Cells; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000378:metabolism; D013662:Tea / Q000737:chemistry
D013662:Tea; D002392:Catechin; C045651:epigallocatechin gallate; D000263:Adenylate Kinase