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: Takato Ueno, Takuji Torimura, Toru Nakamura, Ramadoss Sivakumar, Hitomi Nakayama, Syuichi Otabe, Xiaohong Yuan, Kentaro Yamada, Osamu Hashimoto, Kinya Inoue, Hironori Koga, Michio Sata
• Journal: International journal of molecular medicine (Int J Mol Med) Vol. 24 Issue 1 Pg. 17-22 (Jul 2009) ISSN: 1107-3756 [Print] Greece
• PMID: 19513529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Insulin Receptor Substrate Proteins
• Sterol Regulatory Element Binding Protein 1
• 8-Hydroxy-2'-Deoxyguanosine
• Catechin
• epigallocatechin gallate
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Adipose Tissue (metabolism)
• Animals
• Catechin (analogs & derivatives, therapeutic use)
• Deoxyguanosine (analogs & derivatives, metabolism)
• Fatty Liver (drug therapy, metabolism, pathology)
• Insulin Receptor Substrate Proteins (metabolism)
• Insulin Resistance
• Liver (drug effects, metabolism, pathology)
• Mice
• Mice, Transgenic
• Sterol Regulatory Element Binding Protein 1 (biosynthesis)