Glut5 Knockdown in the Nucleus Tractus Solitarii Alleviates Fructose-Induced Hypertension in Rats. Issue 2 (23rd October 2021)

• Record Type: Journal Article
• Authors: Wu, Chieh-Jen; Cheng, Pei-Wen; Kung, Ming-Hsiang; Ho, Chiu-Yi; Pan, Jun-Yen; Tseng, Ching-Jiunn; Chen, Hsin-Hung
• Is Part Of: Journal of nutrition. Volume 152:Issue 2(2022)
• Page Start: 448
• Page End: 457
• Publication Date: 2021-10-23
• Subjects: fructose -- glucose transporter 5 -- hypertension -- nucleus tractus solitarii -- reactive oxygen species -- metabolic syndrome -- insulin resistance; Nutrition -- Periodicals; Diet -- Periodicals; 613.205
• DOI: 10.1093/jn/nxab374
• Languages: English
• ISSNs: 0022-3166

Abstract

ABSTRACT: Background: Several studies have suggested mechanisms whereby excessive fructose intake increases blood pressure (BP). Glucose transporter 5 (GLUT5) is a fructose transporter expressed on enterocytes, and its involvement in the nucleus tractus solitarius (NTS)–modulated increase in BP following fructose intake remains unclear. Objectives: Herein, we investigated whether NTS Glut5 knockdown (KD) can alleviate fructose-induced hypertension in rat models. Methods: Male Wistar-Kyoto rats (6–8 weeks old; average weight: 230 g) were randomly assigned into 4 groups [control (Con), fructose (Fru), fructose + scrambled (Fru + S), and Fru + KD]. The Con group rats had ad libitum access to regular water, and the other 3 groups were provided 10% fructose water ad libitum for 4 weeks (2 weeks before lentiviral transfection in the Fru + S and Fru + KD groups). Glut5 short hairpin RNA was delivered into the NTS of rats using a lentivirus system. Fructose-induced hypertension was assessed via the tail-cuff technique, a noninvasive blood pressure measurement approach. GLUT5-associated and other insulin signaling pathways in the NTS of rats were assessed using immunofluorescence and immunoblotting analyses. We evaluated between-group differences using the Mann-Whitney U test or Kruskal-Wallis 1-way ANOVA. Results: Compared with the Fru + S group, the Fru + KD group had reduced sympathetic nerve hyperactivity (48.8 ± 3.2 bursts/min; P < 0.05), improved central insulin signaling, upregulated protein kinase B (AKT; 3.0-fold) and neuronal NO synthase (nNOS; 2.78-fold) expression, and lowered BP (17 ± 1 mmHg, P < 0.05). Moreover, Glut5 KD restored signaling dependent on adenosine 5′-monophosphate–activated protein kinase and reduced fructose-induced oxidative stress 2.0-fold, and thus decreased NAD(P)H oxidase in p67-phox 1.9-fold within the NTS. Conclusions: Fructose-induced reactive oxygen species generates in the NTS of rats through GLUT5 and receptor for advanced glycation end products signaling, thus impairing the AKT–nNOS–NO signaling pathway and ultimately causing hypertension.