Epigallocatechin-3-gallate improves nonalcoholic steatohepatitis model mice expressing nuclear sterol regulatory element binding protein-1c in adipose tissue.
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.
Ueno
Takato
T
Research Center for Innovative Cancer Therapy, Kurume University, Kurume, 830-0011, Japan. takato@med.kurume-u.ac.jp
Torimura
Takuji
T
Nakamura
Toru
T
Sivakumar
Ramadoss
R
Nakayama
Hitomi
H
Otabe
Syuichi
S
Yuan
Xiaohong
X
Yamada
Kentaro
K
Hashimoto
Osamu
O
Inoue
Kinya
K
Koga
Hironori
H
Sata
Michio
M
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*
D055504:Insulin Receptor Substrate Proteins; D051780:Sterol Regulatory Element Binding Protein 1; D000080242:8-Hydroxy-2'-Deoxyguanosine; D002392:Catechin; C045651:epigallocatechin gallate; D003849:Deoxyguanosine