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HMGB1‐TLR4 in The Brainstem Nuclei Mediates Fructose‐induced Metabolic Syndrome
Author(s) -
Ho Chiu-Yi,
Chen Hsin-Hung,
Cheng Pei-Wen,
Lin Yu-Te,
Tseng Chin-Jiuun
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.03233
Subject(s) - medicine , tlr4 , endocrinology , metabolic syndrome , fructose , tlr2 , blood pressure , inflammation , hmgb1 , insulin resistance , chemistry , insulin , diabetes mellitus , biochemistry
The metabolic syndrome caused by excessive consumption of fructose is one of a variety of abnormal physiological phenomena, which is related to cardiovascular diseases. Our previous study reported that hypertension and central insulin resistance in WKY rats were caused by fructose intake. Several studies have been reported that the intake of fructose causes central inflammation. Toll‐like receptor 4 (TLR4) play a key role of innate immune signaling and has been implicated in fructose‐induced metabolic syndrome rats. We analyzed systolic blood pressure, biochemical parameter, and TLR4‐signaling pathway of WKY rats and fructose‐intake rats treated with vehicle or CLI‐095 (12 mg×d −1 for 14 days through osmotic mini‐pump). We found that the systolic blood pressure of rats treated CLI‐095 was improved to the normotensive group. The body weight change was recovered to the rats treated with the vehicle. Serum glucose treated with CLI‐095 was restored and stabilized compared with the fructose group. Immunoblotting results showed HMGB1 and TLR4 rather than TLR2, TLR7, TLR9 were induced in the brainstem nuclei area. MyD88, phosphorylated TGF beta‐activated kinase 1 (TAK1) and JNK were inhibited in the CLI‐095 group. Neuroinflammatory indicator iNOS was reduced in the therapy group. These data demonstrated that TLR4 in the central brain participates in the regulation of blood pressure, glucose, and body weight, which suggested HMGB1‐TLR4 might be a potential target for therapeutic interventions in the condition with metabolic syndrome combined with neuroinflammation. Support or Funding Information This work was supported by the Ministry of Science and Technology grants 107‐2320‐B‐075B‐001 (to P.W.C.) and 107‐2320‐B‐075B‐002‐MY2 (to C.J.T.) and Kaohsiung Veterans General Hospital grants VGHKS108‐162 (to Y.T.L.) and VGHUST108‐G3‐1‐3 (to Y.T.L.).