Meteorin-like/Metrnl: A pleiotropic cytokine implicated in metabolic, inflammatory and malignant disorders

Metrnl, a secreted protein highly expressed in adipocytes, endothelial cells, muscle cells, and activated macrophages, has been identified as a novel myokine and adipokine. It plays important roles in enhancing white fat browning, improving insulin sensitivity, modulating glucose homeostasis and regulating inflammatory response. These studies suggest that Metrnl could be a promising biomarker and a potential therapeutic target for the related diseases. However, it is worth noting that there are still several controversies persist within its research field: 1. Metrnl concentrations in patients with type 2 diabetes and obesity yield conflicting results, which has raised doubts about the precise role and reliable application of Metrnl as a biomarker in metabolic diseases; 2. Metrnl exhibits a dual nature that is dependent on specific environments, with both anti-inflammatory and proinflammatory functions; 3.Exercise-induced Metrnl can bring about systemic metabolic benefits, but the CD8⁺ T cell -derived Metrnl impairs anti-tumor effects, raising a critical concern about the potential effects of exercise-induced Metrnl on cancer progression. Therefore, this review would explore those significant controversies and conflicting results surrounding the function and clinical relevance of Metrnl, and proposes future research directions to utilize the therapeutic potential of Metrnl in metabolic and inflammatory and malignant disorders.