PMID- 34687200
OWN - NLM
STAT- MEDLINE
DCOM- 20220221
LR  - 20230216
IS  - 1541-6100 (Electronic)
IS  - 0022-3166 (Linking)
VI  - 152
IP  - 2
DP  - 2022 Feb 8
TI  - Glut5 Knockdown in the Nucleus Tractus Solitarii Alleviates Fructose-Induced 
      Hypertension in Rats.
PG  - 448-457
LID - 10.1093/jn/nxab374 [doi]
AB  - 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.
CI  - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the 
      American Society for Nutrition.
FAU - Wu, Chieh-Jen
AU  - Wu CJ
AD  - Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Veterans 
      General Hospital, Kaohsiung, Taiwan.
AD  - Department of Optometry, Shu-Zen Junior College of Medicine and Management, 
      Kaohsiung, Taiwan.
FAU - Cheng, Pei-Wen
AU  - Cheng PW
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
AD  - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, 
      Taiwan.
FAU - Kung, Ming-Hsiang
AU  - Kung MH
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
FAU - Ho, Chiu-Yi
AU  - Ho CY
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
AD  - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, 
      Taiwan.
FAU - Pan, Jun-Yen
AU  - Pan JY
AD  - Division of Cardiovascular Surgery, Department of Surgery, Kaohsiung Veterans 
      General Hospital, Kaohsiung, Taiwan.
FAU - Tseng, Ching-Jiunn
AU  - Tseng CJ
AUID- ORCID: 0000-0001-5432-9897
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
AD  - Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung, 
      Taiwan.
AD  - Department of Medical Research, China Medical University Hospital, China Medical 
      University, Taichung, Taiwan.
FAU - Chen, Hsin-Hung
AU  - Chen HH
AUID- ORCID: 0000-0002-5662-5945
AD  - Department of Medical Education and Research, Kaohsiung Veterans General 
      Hospital, Kaohsiung, Taiwan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Nutr
JT  - The Journal of nutrition
JID - 0404243
RN  - 30237-26-4 (Fructose)
SB  - IM
MH  - Animals
MH  - Blood Pressure
MH  - Fructose/adverse effects/metabolism
MH  - *Hypertension/chemically induced
MH  - Male
MH  - Rats
MH  - Rats, Inbred WKY
MH  - *Solitary Nucleus/metabolism
OTO - NOTNLM
OT  - fructose
OT  - glucose transporter 5
OT  - hypertension
OT  - insulin resistance
OT  - metabolic syndrome
OT  - nucleus tractus solitarii
OT  - reactive oxygen species
EDAT- 2021/10/24 06:00
MHDA- 2022/02/22 06:00
CRDT- 2021/10/23 08:34
PHST- 2021/06/23 00:00 [received]
PHST- 2021/09/30 00:00 [revised]
PHST- 2021/10/20 00:00 [accepted]
PHST- 2021/10/24 06:00 [pubmed]
PHST- 2022/02/22 06:00 [medline]
PHST- 2021/10/23 08:34 [entrez]
AID - S0022-3166(22)00534-X [pii]
AID - 10.1093/jn/nxab374 [doi]
PST - ppublish
SO  - J Nutr. 2022 Feb 8;152(2):448-457. doi: 10.1093/jn/nxab374.