Fructose Causes Neuroinflammation in the Central Neuronal System may through CX3CL1-CX3CR1 axis to Mediate NO production in Fructose-fed Hypertensive Rat

[Speaker] Chiu-Yi Ho:1,2
[Co-author] Pei-Wen Cheng:1, Shin-Hung Chen:1, Ching-Jiunn Tseng:1,2
1:Department of Medical Education and Research, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, 2:Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

 Hypertension is a risk factor for several cardiovascular disease, such as stroke, myocardial infarction, and heart failure. Our previous studies demonstrated that fructose inhibit NO release through P-AktS473-P-nNOSS1416 pathway in the nucleus tractus solitarii (NTS), leading to increased blood pressure (BP). Evidence suggests that long-term intake of fructose increase the sterile inflammatory response, producing mRNA level of proinflammatory cytokines (e.g. IL-1beta, IL-6, TNF-alpha) in central nervous system (CNS). Furthermore, neuroinflammation is known to be associated with hypertension; however, the mechanism is still unclear. Therefore, this study is to determine whether NO release will be inhibited through neuroinflammatory response in the CNS of fructose-induced hypertension. The hypertensive group were fed with 10% fructose for 1, 2, or 4 weeks respectively. Systolic blood pressure was measured by tail-cutoff method. Immunoblotting or immunohistochemistry analyses were used to quantify protein expression levels of inflammatory cytokines or signal pathway. After that, we treated fructose-induced hypertensive rat by intracerebroventricular infusion of AZD8797 (CX3CR1 antagonist) via osmotic minipump for 2 weeks. In our results, we found the IL-1beta, IL-6, CX3CL1 and CX3CR1 have high expression levels in the NTS and blood pressure (BP) increased significantly after fructose feeding for 2 weeks. However, the BP restores to normal level after administration of AZD8797 groups. Besides, the protein level of P-AktS473 and P-nNOSS1416 showed a significant recovery in the AZD8797 group compared to the fructose-vehicle group. These findings suggest that fructose induced hypertension may through CX3CL1-CX3CR1 caused neuroinflammation which induced P-AktS473-P-nNOSS1416 pathway defect in the central neuronal system. Based on our findings, there is a novel link between hypertension and neuronal inflammation that could be targeted for treatment of cardiometabolic diseases.
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