The Rheumatism Research Center, Catholic Research Institute of Medical Science, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Division of Hepatology, Department of Internal Medicine, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, Republic of Korea.
Exp Mol Med. 2018 Jan 26;50(1):e432. doi: 10.1038/emm.2017.245.
Rheumatoid arthritis (RA) is a systemic autoimmune disease involving excessive inflammation. Recently, RA associated with a metabolic disorder was revealed to be non-responsive to RA medications. Metformin has been reported to have a therapeutic effect on RA and obesity. The aim of this investigation was to study the therapeutic effect and the underlying mechanism of metformin's action in an experimental model of collagen-induced arthritis (CIA) associated with obesity. Metformin was administered daily for 13 weeks to mice with CIA that had been fed a high-fat diet. Metformin ameliorated the development of CIA in obese mice by reducing autoantibody expression and joint inflammation. Furthermore, metformin decreased the expression levels of pSTAT3 and pmTOR and had a small normalizing effect on the metabolic profile of obese CIA mice. In addition, metformin increased the production of pAMPK and FGF21. Metformin also induced the differentiation of brown adipose tissue (BAT), which led to a reciprocal balance between T helper (Th) 17 and regulatory T (Treg) cells in vitro and in vivo. These results suggest that metformin can dampen the development of CIA in obese mice and reduce metabolic dysfunction by inducing BAT differentiation. Thus, metformin could be a therapeutic candidate for non-responsive RA.
类风湿关节炎（RA）是一种全身性自身免疫性疾病，涉及过度炎症。最近，与代谢紊乱相关的 RA 被发现对 RA 药物无反应。二甲双胍已被报道对 RA 和肥胖具有治疗作用。本研究旨在研究二甲双胍在肥胖相关性胶原诱导关节炎（CIA）实验模型中的治疗作用及其作用机制。在给予高脂肪饮食的 CIA 肥胖小鼠中，每天给予二甲双胍治疗 13 周。二甲双胍通过降低自身抗体表达和关节炎症改善了肥胖小鼠 CIA 的发展。此外，二甲双胍降低了 pSTAT3 和 pmTOR 的表达水平，并对肥胖 CIA 小鼠的代谢谱产生了微小的正常化作用。此外，二甲双胍增加了 pAMPK 和 FGF21 的产生。二甲双胍还诱导棕色脂肪组织（BAT）的分化，这导致体外和体内 Th17 和调节性 T（Treg）细胞之间的反向平衡。这些结果表明，二甲双胍可以通过诱导 BAT 分化来抑制肥胖小鼠 CIA 的发展并减轻代谢功能障碍。因此，二甲双胍可能是一种治疗非反应性 RA 的候选药物。
