Branched-chain amino acid deficiency stabilizes insulin-induced vascular endothelial growth factor mRNA in hepatocellular carcinoma cells

Journal of Cellular Biochemistry
Satoshi MiumaKazuhiko Nakao

Abstract

Abnormal sugar metabolism is closely related to chronic liver diseases, including hepatocellular carcinoma (HCC). We previously reported that fasting hyperinsulinemia is a poor prognostic factor for HCC patients. A recent large-scale study has shown that long-term 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-insulin culture conditions, and examined the effect of BCAA on VEGF expression. VEGF secretion was significantly increased by 200 nM of insulin under BCAA deficient conditions, but it was repressed by the addition of BCAA. BCAA activated the mTOR pathway and increase HIF-1α expression under high-insulin culture conditions, however quantitative PCR analysis showed that insulin-induced expression of VEGF mRNAs (VEGF121 and VEGF165) decreased 2 h after the addition of BCAA. The half-lives 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 expressio...Continue Reading

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Citations

Nov 28, 2013·World Journal of Gastroenterology : WJG·Kazuto Tajiri, Yukihiro Shimizu
Jul 12, 2014·Chemico-biological Interactions·Yuanyuan LiWenyuan Gao
Aug 16, 2013·Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition·Takumi KawaguchiMichio Sata
Jan 9, 2019·International Ophthalmology·Ayhan SaglikMuslum Toptan
Apr 3, 2020·The British Journal of Nutrition·Wan-Shui YangYong-Bing Xiang
Dec 5, 2020·Critical Reviews in Food Science and Nutrition·Luigi BarreaUNKNOWN Obesity Programs of nutrition, Education, Research and Assessment (OPERA) group

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