Zc3h10, a CCCH-type zinc finger protein, functions as a transcription factor. It is involved in pathways related to adipogenesis, thermogenesis, and mitochondrial regulation, and is of great biological importance in energy metabolism and related physiological processes. Genetic models, such as gene knockout models, are valuable for studying its functions [1-3].

In mice, Zc3h10 ablation in UCP1+ cells impairs thermogenic capacity, lowers oxygen consumption, and leads to weight gain, indicating its critical role in the thermogenic gene program [1]. In preadipocytes, Zc3h10 depletion results in increased protein translation, impaired F-actin remodeling, mitochondrial and metabolic dysfunction, and negatively affects differentiation into mature adipocytes [2]. A loss-of-function mutation of Zc3h10 in humans is associated with increased body mass index, fat mass, fasting glucose, and triglycerides, and isolated cells from homozygotic individuals display mitochondrial dysfunction [3]. In Chinese native cattle, ZC3H10 knockout dysregulated pathways involved in thermogenesis and immunity, and affected genes related to glucose and lipid metabolism, suggesting its role in cold adaptation [4].

In conclusion, Zc3h10 is fundamental in regulating adipogenesis, thermogenesis, and mitochondrial function. Studies using gene knockout models in mice and cattle have revealed its significance in obesity-related diseases and cold adaptation, providing potential targets for obesity therapeutics and breeding strategies to combat cold climate effects [1,2,3,4].

References:

1. Yi, Danielle, Dempersmier, Jon M, Nguyen, Hai P, Wang, Yuhui, Sul, Hei Sook. . Zc3h10 Acts as a Transcription Factor and Is Phosphorylated to Activate the Thermogenic Program. In Cell reports, 29, 2621-2633.e4. doi:10.1016/j.celrep.2019.10.099. https://pubmed.ncbi.nlm.nih.gov/31775033/

2. Audano, Matteo, Pedretti, Silvia, Ligorio, Simona, De Fabiani, Emma, Mitro, Nico. . Zc3h10 regulates adipogenesis by controlling translation and F-actin/mitochondria interaction. In The Journal of cell biology, 220, . doi:10.1083/jcb.202003173. https://pubmed.ncbi.nlm.nih.gov/33566069/

3. Audano, Matteo, Pedretti, Silvia, Cermenati, Gaia, De Fabiani, Emma, Mitro, Nico. 2018. Zc3h10 is a novel mitochondrial regulator. In EMBO reports, 19, . doi:10.15252/embr.201745531. https://pubmed.ncbi.nlm.nih.gov/29507079/

4. Wang, Luyu, Gao, Yaping, Wang, Jinpeng, Yang, Ling, Huang, Jinming. 2022. Selection Signature and Nuclease technology-Mediated Gene Knockout Analyses Reveal ZC3H10 Involved in Cold Adaptation in Chinese Native Cattle. In Genes, 13, . doi:10.3390/genes13101910. https://pubmed.ncbi.nlm.nih.gov/36292795/