title: Epigallocatechin-3-O-gallate (EGCG) attenuates FFAs-induced peripheral insulin resistance through AMPK pathway and insulin signaling pathway in vivo.
abstract: We aimed to investigate the effects and possible mechanisms of Epigallocatechin-3-O-gallate (EGCG) on free fatty acids (FFAs)-induced peripheral insulin resistance in vivo. Overnight-fasted Wistar rats were subjected to 48-h intravenous infusion of either saline or Intralipid plus heparin (IH) with or without different doses of EGCG co-injection. Hyperinsulinemic-euglycemic clamp was performed in awake rats to assess peripheral insulin sensitivity. Co-injection with EGCG significantly prevented FFAs-induced peripheral insulin resistance, decreased plasma markers of oxidative stress: malondialdehyde (MDA) and 8-isoprostaglandin, and increased antioxidant enzymes: superoxide dismutases (SOD) and Glutathione peroxidase (GPx). Furthermore, EGCG treatment reversed IH-induced: (1) decrease in Thr172 phosphorylation of AMP activated protein kinase (AMPK); (2) increase in protein kinase Cθ(PKCθ) membrane translocation and Ser307 phosphorylation of insulin receptor substrate-1 (IRS-1); (3) decrease in Ser473 phosphorylation of Akt and Glucose transporter 4 (GLUT4) translocation in skeletal muscle and adipose tissue. Our data suggest that EGCG treatment ameliorated FFAs-induced peripheral insulin resistance in vivo, and this might be through decreasing oxidative stress and PKCθ membrane translocation, activating the AMPK pathway and improving insulin signaling pathway in vivo. This study suggests the therapeutic value of EGCG in protecting from insulin resistance caused by elevated FFAs.
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: measme@126.com.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: Zhaosheng@126.com.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Affiliated Fourth Hospital, China Medical University, Shenyang 110032, China. Electronic address: happy2000-3000@163.com.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Medical Record, The First Hospital of China Medical University, Shenyang 110001, China. Electronic address: Zopey_li@126.com.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhao
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: hb3h@hotmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: He
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: zgsysj@hotmail.com.
authors.forename: Na
authors.initials: N
authors.lastname: Wu
authors.affiliation: Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang 110004, China. Electronic address: hpdoctor@hotmail.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Han
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005230:Fatty Acids, Nonesterified / Q000494:pharmacology*; D015309:Glucose Clamp Technique; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D018384:Oxidative Stress; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D005230:Fatty Acids, Nonesterified; D007328:Insulin; D002392:Catechin; C045651:epigallocatechin gallate; D011493:Protein Kinase C; D055372:AMP-Activated Protein Kinases