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

• DOI: 10.1016/j.jlr.2025.100746
• Publication Date: 2025-01-22T00:47:30Z
• Authors: Beibei Chen; Ruixia Bao; Jujie Pan; Zicheng Zhu; Qian Chen; Dan Wang; Yuzheng Wu; Haiyang Yu; Yi Zhang; Tao Wang
• Keywords: HMGCR; adenosine A2A receptor; cholesterol; hyperuricemia; QD415-436; taurine; Biochemistry

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.