Song Meng-Ke, Gu Meng-Fan, Liu Ling, He Lian-Jun, Ye Peng, Yang Kui, Wang Dan-Dan, Olatunji Opeyemi Joshua, Yin Qin, Zuo Jian
Xin'an Medicine Research Center, the First Affiliated Hospital of Wannan Medical College (Yijishan Hospital), No 2, West Zheshan Road, Wuhu, Anhui, 241000, China.
Department of Pharmacy, the Second Affiliated Hospital of Wannan Medical College, No 10, Kangfu Road, Wuhu, Anhui, 241000, China.
Arthritis Res Ther. 2025 Jan 25;27(1):16. doi: 10.1186/s13075-025-03483-1.
Metabolism alteration is a common complication of rheumatic arthritis (RA). This work investigated the reason behind RA-caused triglyceride (TG) changes.
Fresh RA patients' whole blood was transfused into NOD-SCID mice. Metabolism-regulatory tissues were examined after sacrifice. To verify the findings, tissues of the rats with long-lasting adjuvant-induced arthritis (AIA) were analyzed. Some rats were injected with human plasma and GPIHBP1, and their blood TG was monitored. Various cells were stimulated by cytokines or rheumatic subjects' serum. Some pre-adipocytes were cultured by human serum or in the presence of HUVEC cells and GPIHBP1.
TG decrease occurred in blood and white adipose tissues (WAT) of the RA blood-transfused NOD-SCID mice and chronic AIA rats. Fatty acids (FA) oxidation in muscles was accelerated a bit, while TG catabolism status in their livers was varied. TNF-α, IL-1β, IL-6 and RA/AIA serum promoted expression of TG utilization-related enzymes and FA uptake transporters in pre-adipocytes, but barely affected LPL. Mild IL-6 stimulus promoted GPIHBP1 release of HUVEC cells. GPIHBP1 was increased in RA serum. This change can decrease blood TG in rats, which was overshadowed by an injection of excessive GPIHBP1. RA serum slightly inhibited LPL secretion in pre-adipocytes. Both HUVEC cells co-culture and GPIHBP1 supplement reduced LPL distribution on pre-adipocytes, and eliminated LPL activity difference between normal and RA serum-treated cells. No TG uptake difference was observed in these circumstances.
RA-associated inflammation induces GPIHBP1 secretion of endothelial cells, which facilitates blood TG hydrolysis and uptake to compensate the loss in WAT.
代谢改变是类风湿性关节炎（RA）的常见并发症。本研究调查了RA导致甘油三酯（TG）变化的原因。
将新鲜的RA患者全血输注到NOD-SCID小鼠体内。处死小鼠后检查代谢调节组织。为验证研究结果，分析了长期佐剂诱导性关节炎（AIA）大鼠的组织。给一些大鼠注射人血浆和GPIHBP1，并监测其血液TG水平。用细胞因子或风湿患者血清刺激各种细胞。一些前脂肪细胞用人血清或在人脐静脉内皮细胞（HUVEC）和GPIHBP1存在的情况下进行培养。
输注RA患者血液的NOD-SCID小鼠以及慢性AIA大鼠的血液和白色脂肪组织（WAT）中出现TG降低。肌肉中的脂肪酸（FA）氧化略有加速，而其肝脏中的TG分解代谢状态有所不同。肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）以及RA/AIA血清促进前脂肪细胞中TG利用相关酶和FA摄取转运蛋白的表达，但对脂蛋白脂肪酶（LPL）影响不大。轻度IL-6刺激促进HUVEC细胞释放GPIHBP1。RA血清中GPIHBP1增加。这种变化可降低大鼠血液TG水平，但过量注射GPIHBP1可掩盖此作用。RA血清略微抑制前脂肪细胞中LPL的分泌。HUVEC细胞共培养和补充GPIHBP1均减少LPL在前脂肪细胞上的分布，并消除正常血清和RA血清处理细胞之间的LPL活性差异。在这些情况下未观察到TG摄取差异。
RA相关炎症诱导内皮细胞分泌GPIHBP1，这有助于血液TG水解和摄取，以补偿WAT中的损失。
