Branched-chain amino acids suppress insulin-resistance-based hepatocarcinogenesis in obese diabetic rats.
BACKGROUND
Branched-chain amino acids (BCAAs) reportedly inhibit the incidence of hepatocellular carcinoma (HCC) in patients with liver cirrhosis and obesity that is frequently associated with insulin resistance (IR). However, the possible mechanism is still obscure. The aim of the present study was to examine the effect of BCAAs, especially in conjunction with angiogenesis, on hepatocarcinogenesis under the condition of IR.


METHODS
The effect of BCAAs on the development of liver enzyme-altered preneoplastic lesions and angiogenesis was examined in obese diabetic Otsuka Long-Evans Tokushima Fatty rats. We also performed an in vitro study to elucidate the possible mechanisms involved.


RESULTS
Treatment with BCAAs markedly inhibited glutathione-S-transferase placental form (GST-P)-positive preneoplastic lesions along with suppression of neovascularization in the liver. The hepatic expression of vascular endothelial growth factor (VEGF), a potent angiogenic factor, was also attenuated. BCAA treatment significantly suppressed glucose- and insulin-induced in vitro angiogenesis in the presence of VEGF.


CONCLUSIONS
In obese diabetic rats BCAAs exerted a chemopreventive effect against HCC, associated with the suppression of VEGF expression and hepatic neovascularization. Since BCAA preparations are widely used in clinical practice for patients with chronic liver diseases, this agent may represent a new strategy for chemoprevention against HCC in the future.
Yoshiji
Hitoshi
H
Third Department of Internal Medicine, Nara Medical University, Kashihara, Nara, Japan. yoshijih@naramed-u.ac.jp
Noguchi
Ryuichi
R
Kitade
Mitsuteru
M
Kaji
Kosuke
K
Ikenaka
Yasuhide
Y
Namisaki
Tadashi
T
Yoshii
Junichi
J
Yanase
Koji
K
Yamazaki
Masaharu
M
Tsujimoto
Tatsuhiro
T
Akahane
Takemi
T
Kawaratani
Hideto
H
Uemura
Masahito
M
Fukui
Hiroshi
H