Metrnl, also known as Meteorin-like, Cometin, Subfatin, Interleukin-39, Interleukin-41, Meteorin-β, and Metrn-β/Metrnβ, is a widely distributed secreted protein. It is involved in regulating glucose and lipid metabolism, maintaining cardiovascular system homeostasis, and plays roles in inflammation, immunology, and metabolism [3,4]. It can activate multiple intracellular signaling pathways in various cell types like adipocytes, macrophages, myocytes and cardiomyocytes [5].

In studies on diabetic cardiomyopathy, plasma Metrnl levels, myocardial Metrnl protein and mRNA expressions were downregulated in streptozotocin-induced (T1D) and leptin receptor deficiency (db/db) (T2D) mice. Cardiac-specific overexpression of Metrnl ameliorated cardiac injury and dysfunction in T1D and T2D mice, while specific deletion in the heart had the opposite phenotypes. Mechanistically, Metrnl activated the autophagy pathway and inhibited the cGAS/STING signaling in a LKB1/AMPK/ULK1-dependent mechanism [1]. In D-galactose-induced aging mice, Metrnl knockout did not affect baseline cognitive functions but aggravated cognitive impairment in aging mice, along with reduced hippocampal BDNF, TrkB, and GFAP levels [2].

In conclusion, Metrnl is crucial for regulating various biological processes. The use of gene knockout (KO) mouse models has revealed its significance in diseases such as diabetic cardiomyopathy and age-related cognitive dysfunction, highlighting its potential as a therapeutic target for these conditions.

References:

1. Lu, Qing-Bo, Ding, Yi, Liu, Yao, Zhang, Ji-Ru, Sun, Hai-Jian. 2022. Metrnl ameliorates diabetic cardiomyopathy via inactivation of cGAS/STING signaling dependent on LKB1/AMPK/ULK1-mediated autophagy. In Journal of advanced research, 51, 161-179. doi:10.1016/j.jare.2022.10.014. https://pubmed.ncbi.nlm.nih.gov/36334887/

2. Hong, Chen, Wang, Zhi, Zheng, Si-Li, Zhao, Yan, Miao, Chao-Yu. 2022. Metrnl regulates cognitive dysfunction and hippocampal BDNF levels in D-galactose-induced aging mice. In Acta pharmacologica Sinica, 44, 741-751. doi:10.1038/s41401-022-01009-y. https://pubmed.ncbi.nlm.nih.gov/36229598/

3. Dong, Wen-Sheng, Hu, Can, Hu, Min, Ye, Yun-Jia, Zhang, Xin. 2024. Metrnl: a promising biomarker and therapeutic target for cardiovascular and metabolic diseases. In Cell communication and signaling : CCS, 22, 389. doi:10.1186/s12964-024-01767-8. https://pubmed.ncbi.nlm.nih.gov/39103830/

4. Li, Zhuoqi, Gao, Ziyu, Sun, Tao, Zheng, Meilin, Shen, Hui. 2023. Meteorin-like/Metrnl, a novel secreted protein implicated in inflammation, immunology, and metabolism: A comprehensive review of preclinical and clinical studies. In Frontiers in immunology, 14, 1098570. doi:10.3389/fimmu.2023.1098570. https://pubmed.ncbi.nlm.nih.gov/36911663/

5. Alizadeh, Hamid. 2022. Meteorin-like protein (Metrnl): A metabolic syndrome biomarker and an exercise mediator. In Cytokine, 157, 155952. doi:10.1016/j.cyto.2022.155952. https://pubmed.ncbi.nlm.nih.gov/35780711/