title: Green tea polyphenol epigallocatechin-3-gallate ameliorates insulin resistance in non-alcoholic fatty liver disease mice.
abstract: OBJECTIVE
  Epigallocatechin-3-gallate (EGCG) is a major polyphenol in green tea. In this study, we investigated the effects of EGCG on insulin resistance and insulin clearance in non-alcoholic fatty liver disease (NAFLD) mice.
  
  
  METHODS
  Mice were fed on a high-fat diet for 24 weeks. During the last 4 weeks, the mice were injected with EGCG (10, 20 and 40 mg·kg(-1)·d(-1), ip). Glucose tolerance, insulin tolerance and insulin clearance were assessed. After the mice were euthanized, blood samples and tissue specimens were collected. Glucose-stimulated insulin secretion was examined in isolated pancreatic islets. The progression of NAFLD was evaluated histologically and by measuring lipid contents. Insulin-degrading enzyme (IDE) protein expression and enzyme activity were detected using Western blot and immunocapture activity assays, respectively.
  
  
  RESULTS
  The high-fat diet significantly increased the body weight and induced grade 2 or 3 liver fatty degeneration (steatosis, lobular inflammation and ballooning) accompanied by severe hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in the model mice. Administration of EGCG dose-dependently ameliorated the hepatic morphology and function, reduced the body weight, and alleviated hyperlipidemia, hyperglycemia, hyperinsulinemia and insulin resistance in NAFLD mice. Furthermore, EGCG dose-dependently enhanced insulin clearance and upregulated IDE protein expression and enzyme activity in the liver of NAFLD mice.
  
  
  CONCLUSIONS
  EGCG dose-dependently improves insulin resistance in NAFLD mice not only by reducing body weight but also through enhancing the insulin clearance by hepatic IDE. The results suggest that IDE be a potential drug target for the treatment of NAFLD.
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gan
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zi-jun
authors.initials: ZJ
authors.lastname: Meng
authors.affiliation: Department of Rehabilitation, The Third Affiliated Hospital of Southern Medical University, Guangzhou 510630, China.
authors.forename: Ri-bo
authors.initials: RB
authors.lastname: Xiong
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Jin-qiang
authors.initials: JQ
authors.lastname: Guo
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Xiao-cui
authors.initials: XC
authors.lastname: Lu
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Zheng
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Yan-ping
authors.initials: YP
authors.lastname: Deng
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Bing-de
authors.initials: BD
authors.lastname: Luo
authors.affiliation: Department of Occupational Health and Occupational Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zou
authors.affiliation: Experimental Teaching Center of Preventive Medicine, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health and Tropical Medicine, Southern Medical University, Guangzhou 510515, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Li
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D028241:Camellia sinensis; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D007339:Insulysin / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D008517:Phytotherapy; D010946:Plants, Medicinal; D013997:Time Factors
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D002392:Catechin; C045651:epigallocatechin gallate; D007339:Insulysin