2. Academic Validation
  3. Taurine alleviates dysfunction of cholesterol metabolism under hyperuricemia by inhibiting A2AR-SREBP-2/CREB/HMGCR axis

Taurine alleviates dysfunction of cholesterol metabolism under hyperuricemia by inhibiting A2AR-SREBP-2/CREB/HMGCR axis

  • J Lipid Res. 2025 Jan 21;66(2):100746. doi: 10.1016/j.jlr.2025.100746.
Beibei Chen 1,  Ruixia Bao 1,  Jujie Pan 1,  Zicheng Zhu 1,  Qian Chen 1,  Dan Wang 1,  Yuzheng Wu 1,  Haiyang Yu 2,  Yi Zhang 3,  Tao Wang 4
Affiliations

Affiliations

  • 1 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
  • 2 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: hyyu@tjutcm.edu.cn.
  • 3 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China. Electronic address: zhwwxzh@tjutcm.edu.cn.
  • 4 State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: wangtao@tjutcm.edu.cn.
PMID: 39848583 DOI: 10.1016/j.jlr.2025.100746
Abstract

Dysfunctional Cholesterol metabolism is highly prevalent in patients with hyperuricemia. Both uric acid and Cholesterol are independent risk factors for atherosclerosis, contributing to an increased incidence of Cardiovascular Disease in hyperuricemia. Investigating the pathological mechanisms underlying Cholesterol metabolism dysfunction in hyperuricemia is essential. This study identified adenosine and inosine, two major purine metabolites, as key regulators of Cholesterol biosynthesis. These metabolites upregulate 3-hydroxy-3-methylglutaryl-CoA. Further mechanistic studies revealed that adenosine/inosine up-regulated the expression of 3-hydroxy-3-methylglutaryl-CoA by activating adenosine A2A receptor via the Srebp-2/Creb axis in hyperuricemia. Additionally, we found that taurine deficiency contributes to Cholesterol metabolism dysfunction in hyperuricemia. Taurine administration in hyperuricemia mice significantly reduced Cholesterol elevation by inhibiting adenosine A2A receptor. This study provides a promising strategy for treating comorbid hypercholesterolemia and hyperuricemia.

Keywords

HMGCR; adenosine A2A receptor; cholesterol; hyperuricemia; taurine.

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