Metrnl, also known as Meteorin-like, Meteorin-β, Subfatin, Cometin, Interleukin-39, and Interleukin-41, is a novel secreted protein. It is ubiquitously expressed in skeletal muscle, heart, adipose, and renal tubules, and plays pleiotropic roles in inflammation, immunology, and metabolism, such as regulating energy expenditure, glucose and lipid homeostasis, and maintaining cardiovascular system homeostasis. It is involved in pathways like LKB1/AMPK/ULK1-mediated autophagy and Sirt3-AMPK signaling axis [1,2,4,5,6,7]. Genetic models, especially KO/CKO mouse models, are valuable for studying its functions.

In KO mouse models, cardiac-specific deletion of Metrnl exacerbated diabetic cardiomyopathy, with increased cardiac injury and dysfunction, while over-expression alleviated these phenotypes. This was associated with Metrnl's regulation of the cGAS/STING signaling pathway via LKB1/AMPK/ULK1-mediated autophagy [1]. In the context of cognitive function, Metrnl knockout aggravated cognitive impairment in D-galactose-induced aging mice and reduced hippocampal BDNF levels [3].

In conclusion, Metrnl is a crucial secreted protein regulating multiple biological processes. Model-based research, particularly KO/CKO mouse models, has revealed its protective roles in diabetic cardiomyopathy and cognitive function during aging. Understanding Metrnl's functions offers potential therapeutic strategies for related diseases [1,3].

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. Zhou, Yuxia, Liu, Lu, Jin, Bangming, Yan, Rui, Guo, Bing. . Metrnl Alleviates Lipid Accumulation by Modulating Mitochondrial Homeostasis in Diabetic Nephropathy. In Diabetes, 72, 611-626. doi:10.2337/db22-0680. https://pubmed.ncbi.nlm.nih.gov/36812572/

3. 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/

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. 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/

6. Miao, Zhu-Wei, Chen, Jin, Chen, Can-Xin, Zhao, Huan-Yu, Miao, Chao-Yu. 2024. Metrnl as a secreted protein: Discovery and cardiovascular research. In Pharmacology & therapeutics, 263, 108730. doi:10.1016/j.pharmthera.2024.108730. https://pubmed.ncbi.nlm.nih.gov/39401532/

7. Miao, Zhu-Wei, Hu, Wen-Jun, Li, Zhi-Yong, Miao, Chao-Yu. 2020. Involvement of the secreted protein Metrnl in human diseases. In Acta pharmacologica Sinica, 41, 1525-1530. doi:10.1038/s41401-020-00529-9. https://pubmed.ncbi.nlm.nih.gov/32999412/