BACKGROUND: Obesity increases the risk of fatty liver disease and liver cancer. There are several models of obesity-associated hepatocellular carcinoma, but tumor development in these models is slow. MATERIALS AND METHODS: We investigated Zucker fatty rats, a model of obesity and insulin resistance, to discover if diethylnitrosamine (DEN), a potent liver carcinogen, might enhance liver carcinogenesis. We also investigated the effect of branched chain amino acids (BCAA) against the development of liver cancer. RESULTS: Incidence and number of hepatocellular carcinomas and adenomas were significantly greater in DEN-treated Zucker fatty rats than in DEN-treated lean rats. All treated Zucker fatty rats developed hepatocellular carcinoma within 16 weeks. Long-term BCAA supplementation significantly reduced expression of CyclinD1, PCNA, thymidine kinase, Bcl-2, and GST-p and increased expression of p21 in the liver. Furthermore, BCAA treatment significantly reduced the area of GST-p positive foci. CONCLUSION: Long-term BCAA treatment may induces cell cycle arrest and apoptotic induction, thus suppressing pre-neoplastic lesions.
BACKGROUND:Obesity increases the risk of fatty liver disease and liver cancer. There are several models of obesity-associated hepatocellular carcinoma, but tumor development in these models is slow. MATERIALS AND METHODS: We investigated Zucker fatty rats, a model of obesity and insulin resistance, to discover if diethylnitrosamine (DEN), a potent liver carcinogen, might enhance liver carcinogenesis. We also investigated the effect of branched chain amino acids (BCAA) against the development of liver cancer. RESULTS: Incidence and number of hepatocellular carcinomas and adenomas were significantly greater in DEN-treated Zucker fatty rats than in DEN-treated lean rats. All treated Zucker fatty rats developed hepatocellular carcinoma within 16 weeks. Long-term BCAA supplementation significantly reduced expression of CyclinD1, PCNA, thymidine kinase, Bcl-2, and GST-p and increased expression of p21 in the liver. Furthermore, BCAA treatment significantly reduced the area of GST-p positive foci. CONCLUSION: Long-term BCAA treatment may induces cell cycle arrest and apoptotic induction, thus suppressing pre-neoplastic lesions.
Authors: Mahmoud Delphan; Tengda Lin; David B Liesenfeld; Johanna Nattenmüller; Jürgen T Böhm; Biljana Gigic; Nina Habermann; Lin Zielske; Petra Schrotz-King; Martin Schneider; Alexis Ulrich; Hans-Ulrich Kauczor; Cornelia M Ulrich; Jennifer Ose Journal: Metabolomics Date: 2018-01-31 Impact factor: 4.290