Hyperuricemia Inhibition Protects SD Rats Against Fructose-Induced Obesity Hypertension Via Modulation of Inflammation and Renin-Angiotensin System in Adipose Tissue

Exp Clin Endocrinol Diabetes. 2021 Mar;129(4):314-321. doi: 10.1055/a-1023-6710. Epub 2019 Nov 4.

Abstract

Objective: The present study was aimed to reveal the relationship between uric acid and fructose-induced obesity hypertension and its mechanisms.

Methods: 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.

Results: 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.

Conclusion: 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.

MeSH terms

  • Adipose Tissue* / drug effects
  • Adipose Tissue* / immunology
  • Allopurinol / administration & dosage
  • Allopurinol / pharmacology*
  • Animals
  • Benzbromarone / administration & dosage
  • Benzbromarone / pharmacology*
  • Diet, Carbohydrate Loading / adverse effects*
  • Disease Models, Animal
  • Fructose / administration & dosage
  • Fructose / adverse effects*
  • Gout Suppressants / administration & dosage
  • Gout Suppressants / pharmacology*
  • Hypertension* / etiology
  • Hypertension* / prevention & control
  • Hyperuricemia* / blood
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / etiology
  • Inflammation* / blood
  • Inflammation* / etiology
  • Inflammation* / immunology
  • Inflammation* / prevention & control
  • Male
  • Obesity, Abdominal* / chemically induced
  • Obesity, Abdominal* / complications
  • Obesity, Abdominal* / prevention & control
  • Rats
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System*

Substances

  • Gout Suppressants
  • Fructose
  • Benzbromarone
  • Allopurinol