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Taurine alleviates dysfunction of cholesterol metabolism under hyperuricemia by inhibiting A2AR-SREBP-2/CREB/HMGCR
Beibei Chen1, Ruixia Bao1, Jujie Pan1
1State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.
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.
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