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A recent large\u2010scale study has shown that long\u2010term administration of branched chain amino acids (BCAA) reduces the risk of HCC development in obese cirrhotic patients who have been diagnosed with diabetes mellitus, although the mechanism by which it does so is unclear. In this study, we analyzed the expression of vascular endothelial growth factor (VEGF) in HepG2 cells under high\u2010insulin culture conditions, and examined the effect of BCAA on VEGF expression. VEGF secretion was significantly increased by 200\u2009nM of insulin under BCAA deficient conditions, but it was repressed by the addition of BCAA. BCAA activated the mTOR pathway and increase HIF\u20101\u03b1 expression under high\u2010insulin culture conditions, however quantitative PCR analysis showed that insulin\u2010induced expression of VEGF mRNAs (VEGF121 and VEGF165) decreased 2\u2009h after the addition of BCAA. The half\u2010lives of both VEGF121 and 165 mRNAs were shortened in the presence of BCAA compared to the absence of BCAA. Therefore it is thought that BCAA regulate VEGF expression mainly at the post\u2010transcriptional level. We also examined which of the Valine, Leucine, and Isoleucine components of BCAA were essential for VEGF mRNA degradation. All three BCAA components were required for acceleration of insulin\u2010induced VEGF mRNA degradation. These results suggest that administration of BCAA may downregulate VEGF expression in patients who have hyperinsulinemia and are in the process of developing HCC. J. Cell. Biochem. 113: 3113\u20133121, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24188","type":"journal-article","created":{"date-parts":[[2012,5,11]],"date-time":"2012-05-11T15:56:58Z","timestamp":1336751818000},"page":"3113-3121","source":"Crossref","is-referenced-by-count":23,"title":["Branched\u2010chain amino acid deficiency stabilizes insulin\u2010induced vascular endothelial growth factor mRNA in hepatocellular carcinoma 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