title: Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue.
abstract: We examined whether or not epigallocatechin-3-gallate (EGCG) improves liver injury of nonalcoholic steatohepatitis (NASH) model mice expressing nuclear sterol regulatory element-binding protein 1c (nSREBP-1c) in adipose tissue. nSREBP-1c transgenic C57BL6 mice aged 30 weeks were divided into group 1 (no treatment), group 2 (ascorbic acid alone), group 3 (ascorbic acid and 0.05% EGCG), and group 4 (ascorbic acid and 0.1% EGCG). At 42 weeks, we performed measurement of liver weight to body weight, biochemical assays, morphometry of liver specimens, immunohistochemistry for 8-hydro-2'-deoxyguanosine (8-OhdG), and Western blotting for insulin and TNF-alpha signalings. Ratio of liver weight to body weight in the high dose EGCG-treated group (group 4) was significantly lower than those of groups 1 and 2 (p<0.05 and <0.01, respectively). Blood ALT, glucose, total cholesterol, and triglyceride levels of group 4 were significantly low compared with those of the EGCG-non-treated group (groups 1 and 2) (p<0.05, respectively). The degrees of steatosis, inflammation, ballooning hepatocytes and Mallory-Denk bodies in group 4 significantly improved compared with those in other groups (p<0.05, respectively). The 8-OhdG immunolocalization in liver tissues of the group 4 obviously decreased compared with those of groups 2 and 3. For Western blotting, the expressions of insulin receptor substrate-1 (IRS-1) and phosphorylated IRS-1 (pIRS-1) in liver tissues of group 4 increased compared with those of groups 2 and 3. On the other hand, the expressions of pAkt, pIKKbeta and pNF-kappaB decreased compared with those of groups 2 and 3. From these results, EGCG reduces inflammation, insulin resistance and oxidative stress, and suppresses liver injury in nSREBP-1c transgenic mice.
authors.affiliation: Research Center for Innovative Cancer Therapy, Kurume University, Kurume, 830-0011, Japan. takato@med.kurume-u.ac.jp
authors.forename: Takato
authors.initials: T
authors.lastname: Ueno
authors.forename: Takuji
authors.initials: T
authors.lastname: Torimura
authors.forename: Toru
authors.initials: T
authors.lastname: Nakamura
authors.forename: Ramadoss
authors.initials: R
authors.lastname: Sivakumar
authors.forename: Hitomi
authors.initials: H
authors.lastname: Nakayama
authors.forename: Syuichi
authors.initials: S
authors.lastname: Otabe
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Yuan
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Osamu
authors.initials: O
authors.lastname: Hashimoto
authors.forename: Kinya
authors.initials: K
authors.lastname: Inoue
authors.forename: Hironori
authors.initials: H
authors.lastname: Koga
authors.forename: Michio
authors.initials: M
authors.lastname: Sata
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D005234:Fatty Liver / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis*
chemical_list: D055504:Insulin Receptor Substrate Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin; C045651:epigallocatechin gallate; D003849:Deoxyguanosine