The role of consumption of fructose on blood pressure in the nucleus tractus solitarii

• Main Authors: Shu-Wei Wen, 溫書緯
• Other Authors: Ching-Jiunn Tseng
• Format: Others
• Language: en_US
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/5ff7um

碩士 === 國立中山大學 === 生物醫學研究所 === 102 === Metabolic syndrome is one of the leading cause of death. In clinical and previous studies demonstrated that fructose consumption will induce metabolic syndrome such as hyperlipidemia, hyperglycemia, type 2 diabetes mellitus and hypertensive diseases. However, fructose is primarily metabolized through triglyceride synthesis in the liver and that use as an energy source by de novo lipogenesis. To the best of our knowledge, high fructose intake led to blood triglyceride increase significantly and accumulation of triglyceride in the liver. Several studies showed that administration of fructose significantly increase systolic blood pressures (SBP), renal sympathetic nerves activity (RSNA) and significantly decreased baroreflex sensitivity, nitric oxide synthase expression. Previous studies found that fructose uses glucose transport system and is transported into blood by glucose transporter five (GLUT5) and glucose transporter two (GLUT2) in the liver and small intestine. Simultaneous finding, GLUT5 and GLUT2 expression increased significantly in neuronal cell by administration of fructose. Therefore, we postulated that fructose may induces the development of hypertension which is either stimulus for triglyceride or glucose transporters and that is involved in triggering sympathetic overactivation in the nucleus tractus solitarii(NTS). However, the mechanisms of the overactivation in the brain that cause dysfunction of NO in fructose-induced hypertension remained unclear. Male WKY (Wistar Kyoto) rats were fed with 10% fructose water for one week. Systolic blood pressures (SBP), renal sympathetic nerves activity, baroreflex sensitivity and endogenous nitric oxide level in the NTS were determined. Quantitative PCR and immunoblotting analyses were used to quantify gene and protein expression levels. Our data showed that sympathetic nerve activity and systolic blood pressures (SBP) increased significantly. Interestingly, the fructose concentration in the CSF was significantly increased and NO level in the NTS was significantly decreased after administration of fructose for day1 until day7. These changes are blunted by oral gavage of PF-04620110 (DGAT1 inhibitor) decrease level of SBP and triglyceride however, PF-04620110 were not improves SNA and center NO level in the fructose fed rats at day7. Therefore, fructose may be enhancing GLUT5 synthesis and that perhaps transport fructose into brain in the early stage of fructose inducer pressor. The results showed consumption of fructose enhance GLUT5 expression in the NTS of fructose fed rats at day1~day7. Simultaneously, Fructose (500M) treatment induced GLUT5-RAGE-ROS and reduced AKT-nNOS-NO signaling pathway in the PC12 neuronal cell. In conclusion, fructose through GLUT5-RAGE overexpression induces ROS generation in the NTS, which will lead to AKT-nNOS-NO signaling pathway and impairment cause hypertension.