Zhang Shan, Hu Shasha, Tan Haibo, Jia Ertao
Shenzhen Traditional Chinese Medicine Hospital Affiliated to Nanjing University of Chinese Medicine, Shenzhen, PR China.
Shenzhen Traditional Chinese Medicine Hospital, Department of Rheumatism, Shenzhen, PR China.
PLoS One. 2025 Aug 6;20(8):e0328794. doi: 10.1371/journal.pone.0328794. eCollection 2025.
The study aimed to examine the association between obesity and hyperuricemia in ob/ob mice.
An animal model of obesity was developed using male ob/ob mice. Biochemical parameter test kits were used to measure serum uric acid (UA), hepatic xanthine oxidase (XOD) activity, serum creatinine (Scr), serum lipid profiles, and blood urea nitrogen (BUN). Then, liver tissues were collected for hematoxylin and eosin (H&E) staining, flow cytometry, and western blot (WB) analysis. Furthermore, Huh-7 cells were co-cultured with THP-1 macrophages for 24 hours, with or without LPS + IFN-γ or PA, and subsequently analyzed for XOD activity. In addition, the Huh-7 cells stimulated with PA were analyzed by metabolomics and validated by WB and RT-qPCR.
Levels of Serum lipid profiles, UA, and XOD activity are elevated in ob/ob mice. In ob/ob mice, liver M1 macrophage polarization is markedly enhanced. In vitro studies show that elevated XOD activity in hepatocytes during hyperlipidemia does not correlate with M1 macrophage polarization. Metabolomics showed that the XOD activity of hepatocytes in hyperlipidemia may be related to pyruvate metabolism. Moreover, the protein and mRNA levels of pyruvate dehydrogenase (PDH), an enzyme that limits pyruvate accumulation, were significantly down-regulated in Huh-7 cells with PA stimulation.
Hyperuricemia in ob/ob mice relates to hepatocellular pyruvate metabolism/ xanthine oxidase axis.
本研究旨在探讨ob/ob小鼠肥胖与高尿酸血症之间的关联。
使用雄性ob/ob小鼠建立肥胖动物模型。采用生化参数检测试剂盒测量血清尿酸（UA）、肝组织黄嘌呤氧化酶（XOD）活性、血清肌酐（Scr）、血脂谱以及血尿素氮（BUN）。随后，收集肝脏组织进行苏木精-伊红（H&E）染色、流式细胞术和蛋白质免疫印迹（WB）分析。此外，将Huh-7细胞与THP-1巨噬细胞共培养24小时，分别给予或不给予脂多糖（LPS）+干扰素-γ（IFN-γ）或棕榈酸（PA）刺激，随后分析XOD活性。另外，对经PA刺激的Huh-7细胞进行代谢组学分析，并通过WB和逆转录-定量聚合酶链反应（RT-qPCR）进行验证。
ob/ob小鼠的血脂谱、UA水平和XOD活性升高。在ob/ob小鼠中，肝脏M1巨噬细胞极化明显增强。体外研究表明，高脂血症期间肝细胞中XOD活性升高与M1巨噬细胞极化无关。代谢组学显示，高脂血症中肝细胞的XOD活性可能与丙酮酸代谢有关。此外，在PA刺激的Huh-7细胞中，限制丙酮酸积累的丙酮酸脱氢酶（PDH）的蛋白质和mRNA水平显著下调。
ob/ob小鼠的高尿酸血症与肝细胞丙酮酸代谢/黄嘌呤氧化酶轴有关。
