Department of Diabetes, Endocrinology and Clinical Immunology, Hyogo Medical University, 1-1, Mukogawa-cho, Nishinomiya, Hyogo, 663-8501, Japan.
Radioisotope and Chemical Analysis Center, Laboratory Management Department, Sanwa Kagaku Kenkyusho, Nagoya, Japan.
Sci Rep. 2022 Jul 19;12(1):12282. doi: 10.1038/s41598-022-16688-0.
The enzyme xanthine oxidoreductase (XOR) catalyzes the synthesis of uric acid (UA) from hypoxanthine and xanthine, which are products of purine metabolism starting from ribose-5-phosphate. Several studies suggested a relationship between hyperuricemia and hepatic steatosis; however, few previous studies have directly examined the relationship between XOR activity and hepatic steatosis. A total of 223 subjects with one or more cardiovascular risk factors were enrolled. The liver-to-spleen (L/S) ratio on computed tomography and the hepatic steatosis index (HSI) were used to assess hepatic steatosis. We used a newly developed highly sensitive assay based on [C, N] xanthine and liquid chromatography/triple quadrupole mass spectrometry to measure plasma XOR activity. Subjects with the L/S ratio of < 1.1 and the HSI of < 36 had increased XOR activity and serum UA levels. Independent of insulin resistance and serum UA levels, multivariate logistic regression analysis revealed that plasma XOR activity was associated with the risk of hepatic steatosis as assessed by the L/S ratio and HSI. According to the findings of this study, plasma XOR activity is associated with hepatic steatosis independent of insulin resistance and serum UA levels.
黄嘌呤氧化还原酶(XOR)可催化次黄嘌呤和黄嘌呤合成尿酸(UA),而次黄嘌呤和黄嘌呤是从核糖-5-磷酸开始的嘌呤代谢产物。多项研究表明高尿酸血症与肝脂肪变性之间存在关联;然而,之前的研究很少直接检测 XOR 活性与肝脂肪变性之间的关系。共纳入了 223 名具有一个或多个心血管危险因素的受试者。使用计算机断层扫描的肝脾比值(L/S)和肝脂肪变性指数(HSI)来评估肝脂肪变性。我们使用了一种基于[C,N]黄嘌呤和液相色谱/三重四极杆质谱的新的高灵敏度测定法来测量血浆 XOR 活性。L/S 比值<1.1 和 HSI<36 的受试者的 XOR 活性和血清 UA 水平升高。多元逻辑回归分析显示,独立于胰岛素抵抗和血清 UA 水平,血浆 XOR 活性与 L/S 比值和 HSI 评估的肝脂肪变性风险相关。根据本研究的结果,血浆 XOR 活性与肝脂肪变性相关,而与胰岛素抵抗和血清 UA 水平无关。