高尿酸血症
黄嘌呤氧化酶
内科学
尿酸
脂肪肝
内分泌学
医学
危险系数
痛风
脂肪变性
化学
胃肠病学
疾病
置信区间
生物化学
酶
作者
Chengfu Xu,Xingyong Wan,Lei Xu,Honglei Weng,Ming Yan,Min Miao,Yan Sun,Guofan Xu,Steven Dooley,Youming Li,Chaohui Yu
标识
DOI:10.1016/j.jhep.2015.01.019
摘要
Hyperuricemia is a common feature of patients with non-alcoholic fatty liver disease (NAFLD). This study aimed to explore the causal relationship and underlying mechanisms between NAFLD and hyperuricemia.We evaluated the impact of NAFLD on the development of hyperuricemia in a cohort of 5541 baseline hyperuricemia-free individuals. We further analyzed xanthine oxidase (XO), a rate-limiting enzyme that catalyzes uric acid production, as a candidate to link NAFLD and hyperuricemia.In the first study, a 7-year prospective analysis found that NAFLD was strongly associated with subsequent development of hyperuricemia. Cox proportional hazards regression analyses showed that age, gender, and body mass index adjusted hazard ratio (95% confidence interval) for incident hyperuricemia was 1.609 (1.129-2.294) in individuals with NAFLD, as compared with those without NAFLD at baseline. In the second study, we observed that expression and activity of XO were significantly increased in cellular and mouse models of NAFLD. Knocking down XO expression or inhibiting XO activity significantly decreases uric acid production and attenuates free fatty acids-induced fat accumulation in HepG2 cells. Inhibiting XO activity also significantly prevents the development of and ameliorates established hepatic steatosis induced by a high-fat diet in mice. Further experiments indicated that XO regulates activation of the NLRP3 inflammasome, which may be essential for the regulatory effect of XO on NAFLD.NAFLD significantly increases the risk of incident hyperuricemia. XO is a mediator of the relationship between NAFLD and hyperuricemia, and may serve as a novel therapeutic target for the two linked diseases.
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