Department of Endocrinology, Central Theater Command General Hospital of the Chinese PLA, Wuhan, China.
Exp Clin Endocrinol Diabetes. 2021 Mar;129(4):314-321. doi: 10.1055/a-1023-6710. Epub 2019 Nov 4.
The present study was aimed to reveal the relationship between uric acid and fructose-induced obesity hypertension and its mechanisms.
A rat model with obesity hypertension was induced by a high-fructose diet. In the experiment I, the rats were fed with fructose for 8 wks along with allopurinol or benzbromarone at the beginning. In the experiment II, the rats were fed with fructose for 8 wks firstly. And then, these rats were treated with allopurinol or benzbromarone for additional 6 wks.
Fructose-fed rats showed hyperuricemia, abdominal obesity hypertension and an activation in adipose renin-angiotensin system (RAS). Also, fructose-fed rats had higher levels of proinflammatory cytokines and more macrophages infiltrating in adipose tissue. In the experiment I, allopurinol and benzbromarone significantly reduced serum uric acid at 8 wk. Adipose RAS overactivation, adipose inflammatory responses and the development of obesity hypertension were all effectively prevented by hyperuricemia inhibition. In the experiment II, 6-wk treatment with allopurinol and benzbromarone significantly decreased serum uric acid, downregulated adipose RAS, abolished adipose inflammation and improved obesity hypertension.
In conclusion, urate-lowering therapy protects rats against fructose-induced obesity hypertension. The mechanisms appear to be via downregulated adipose RAS and reduced inflammation in adipose tissue.
本研究旨在揭示尿酸与果糖诱导的肥胖高血压的关系及其机制。
采用高果糖饮食诱导肥胖高血压大鼠模型。在实验 I 中，大鼠在开始时同时给予果糖和别嘌醇或苯溴马隆 8 周。在实验 II 中，大鼠首先给予果糖 8 周。然后，这些大鼠再用别嘌醇或苯溴马隆治疗 6 周。
果糖喂养的大鼠出现高尿酸血症、腹部肥胖性高血压和脂肪肾素-血管紧张素系统（RAS）过度激活。此外，果糖喂养的大鼠脂肪组织中促炎细胞因子水平升高，巨噬细胞浸润增加。在实验 I 中，别嘌醇和苯溴马隆在 8 周时显著降低血清尿酸水平。抑制高尿酸血症可有效预防脂肪 RAS 过度激活、脂肪炎症反应和肥胖性高血压的发生。在实验 II 中，别嘌醇和苯溴马隆治疗 6 周可显著降低血清尿酸水平，下调脂肪 RAS，消除脂肪炎症，改善肥胖性高血压。
综上所述，降低尿酸治疗可保护大鼠免受果糖诱导的肥胖高血压的影响。其机制可能是通过下调脂肪 RAS 和减少脂肪组织炎症。
