Metformin ameliorates experimental-obesity-associated autoimmune arthritis by inducing FGF21 expression and brown adipocyte differentiation

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. The diabetes drug metformin helps ease obesity-associated arthritis in a mouse model. Researchers in South Korea, led by Mi-La Cho from the Catholic University of Korea in Seoul, fed a high-fat diet to mice with experimentally induced autoimmune arthritis. They then treated some animals for 13 weeks with metformin, a drug that lowers blood sugar levels. Treatment resulted in decreases in joint inflammation and in other symptoms of arthritis compared to untreated animals. Metformin also altered the profile of immune-related signaling molecules and increased the levels of brown fat. These changes suggested that metformin helped to address both arthritis and metabolic dysfunction in the mice. The findings highlight the potential of using this drug in human patients to treat rheumatoid arthritis related to metabolic disease.