Supplementary Material for: Effects of febuxostat therapy on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia: A randomized controlled study

Introduction: Elevated levels of serum uric acid (SUA) are strongly associated with several components of the metabolic syndrome, particularly obesity. Previous studies have reported the correlation between SUA levels, xanthine oxidoreductase (XOR) activity, and the imbalanced adipokine levels that are characteristic of obesity. In this study, we explored the effect of febuxostat on circulating adipokine profiles in patients with overweight or obesity and asymptomatic hyperuricemia. Methods: This study was a single-center, randomized and controlled clinical trial that enrolled 130 participants with asymptomatic hyperuricemia and obesity. 117 participants were included in the final analysis, with 60 participants in the febuxostat group and 57 in the control group. We compared the circulating adipokine levels at 3 and 6 months, including high molecular weight (HMW) adiponectin, chemerin, omentin, (monocyte chemotactic protein-1) MCP-1, asprosin, fibroblast growth factor 21 (FGF21), neuregulin-4 (Nrg4), leptin, resistin, vaspin, visfatin, adipsin, and assessed the correlation between changes in adipokine levels (Δadipokines) and changes in XOR activity (ΔXOR) after febuxostat treatment. Results: The results showed that an increase in HMW adiponectin and omentin levels and a decrease in chemerin and asprosin levels at 3 or 6 months compared to the control group. Additionally, a positive correlation was observed between ΔXOR activity and Δasprosin. Furthermore, after adjusting for ΔTG (triglyceride) and ΔSUA (serum uric acid) in multiple linear regression analyses, we found that ΔXOR activity was independently correlated with Δasprosin. Conclusion: This study may provide important evidence that febuxostat could alleviate the imbalance in circulating adipokine levels in patients with overweight or obesity and asymptomatic hyperuricemia. Furthermore, we observed a positive correlation between changes in asprosin levels and changes in XOR activity after febuxostat treatment.

引言：血清尿酸（serum uric acid, SUA）水平升高与代谢综合征的多种组分存在显著关联，尤以肥胖最为突出。既往已有研究报道了SUA水平、黄嘌呤氧化还原酶（xanthine oxidoreductase, XOR）活性与肥胖特征性脂肪因子失衡之间的相关性。本研究旨在探讨非布司他（febuxostat）对超重或肥胖伴无症状高尿酸血症患者循环脂肪因子谱的影响。
方法：本研究为单中心随机对照临床试验，共纳入130例无症状高尿酸血症合并肥胖受试者，最终117例完成数据分析，其中非布司他组60例，对照组57例。我们对比了受试者干预后3个月及6个月时的循环脂肪因子水平，检测指标涵盖高分子量（high molecular weight, HMW）脂联素、趋化素（chemerin）、网膜素（omentin）、单核细胞趋化蛋白-1（monocyte chemotactic protein-1, MCP-1）、天冬蛋白素（asprosin）、成纤维细胞生长因子21（fibroblast growth factor 21, FGF21）、神经调节蛋白4（neuregulin-4, Nrg4）、瘦素（leptin）、抵抗素（resistin）、血管丝氨酸蛋白酶抑制剂（vaspin）、内脏脂肪素（visfatin）、脂肪酶素/补体D因子（adipsin）；同时评估了非布司他治疗后脂肪因子水平变化量（Δadipokines）与黄嘌呤氧化还原酶活性变化量（ΔXOR）之间的相关性。
结果：结果显示，相较于对照组，干预后3个月或6个月时，受试者的高分子量脂联素与网膜素水平升高，而趋化素及天冬蛋白素水平降低。此外，ΔXOR活性与Δasprosin水平变化量呈正相关。进一步经多重线性回归分析校正Δ甘油三酯（ΔTG，triglyceride）与Δ血清尿酸（ΔSUA）后，ΔXOR活性仍与Δasprosin独立相关。
结论：本研究可为非布司他改善超重或肥胖伴无症状高尿酸血症患者的循环脂肪因子失衡提供重要依据。此外，本研究还观察到非布司他治疗后，天冬蛋白素水平变化量与黄嘌呤氧化还原酶活性变化量呈正相关。