{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nMETRNL, also known as Subfatin or IL‐41, is a novel secreted protein identified originally using caloric restriction and adipocyte gene screening approaches. It is highly expressed in white adipose tissue and skeletal muscle, where it promotes the differentiation of white adipocytes, enhances lipid metabolism, and improves local insulin sensitivity—actions mediated, at least in part, through activation of the PPARγ pathway. These early studies laid the foundation for understanding its role as an insulin‐sensitizing adipokine."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}]}, {"type": "t", "text": "\n \nDisrupted circulating levels of METRNL have been reported across a spectrum of metabolic and cardiovascular disorders. Clinical investigations have found that lower serum concentrations correlate with coronary artery disease, type 2 diabetes, and endothelial dysfunction while also being linked to adverse inflammatory profiles and insulin resistance. In some cohorts, however, elevated METRNL levels are observed in obesity and type 2 diabetes, pointing to complex, context‐dependent regulation. Altered METRNL levels have additionally been noted in gestational diabetes, polycystic ovary syndrome, and even inflammatory bowel disease—suggesting that this protein may serve as a valuable biomarker reflecting metabolic and inflammatory status."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "12"}]}, {"type": "t", "text": "\n \nBeyond its metabolic actions, METRNL displays an impressive array of functions in tissue remodeling and repair. Experimental evidence in osteoblasts indicates that its ectopic overexpression can inhibit mineralized nodule formation, suggesting an involvement in bone remodeling. In the cardiovascular system, METRNL released from monocytes and macrophages acts as a high‐affinity ligand for the KIT receptor to drive postinfarction angiogenesis and improve infarct repair. Its protective actions extend to the kidney, where enhancing METRNL expression helps maintain mitochondrial homeostasis and alleviate lipid accumulation in diabetic kidney disease. METRNL’s immunomodulatory influence is underscored by altered levels observed in autoimmune and inflammatory disorders such as Graves’ disease, rheumatoid arthritis, systemic sclerosis, and osteoarthritis. Moreover, its detection in breast milk hints at roles in neonatal development, while exercise‐induced upregulation and its increased expression in premalignant and malignant skin lesions suggest additional functions in cardiovascular protection and possible tumor biology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "13", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhi-Yong Li, Si-Li Zheng, Pei Wang, et al. 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