Reg3g, also known as regenerating islet-derived 3 gamma, is an antimicrobial C-type lectin. It functions both within the intestinal lumen and as a gut hormone, linking the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function [1]. It is also involved in the regulation of innate immunity and has been associated with pathways related to inflammation, cell regeneration, and metabolic regulation. Genetic models, especially knockout mice, have been crucial in studying its functions.

In Reg3g knockout mice, the beneficial effects of high-inulin diets and vertical sleeve gastrectomy on gut function, energy balance, and glucose regulation are absent, suggesting that Reg3g is essential for these processes [1]. In the context of ethanol-induced liver disease, engineered bacteria producing IL-22 reduce liver damage by inducing Reg3g expression, but this effect is absent in Reg3g -/- mice, indicating that Reg3g is necessary for protecting against ethanol-induced steatohepatitis [2]. In non-alcoholic steatohepatitis (NASH), decreased expression of reg3g is associated with disease progression. Ileal deficiency in reg3g leads to intestinal barrier damage, endotoxin translocation, and liver fibrosis, while upregulating reg3g expression with Fructus Aurantii (Quzhou origin) ameliorates NASH [3].

In conclusion, Reg3g plays essential roles in multiple biological processes, including those related to the gut-microbiome axis, energy and glucose regulation, and protection against liver diseases. The use of Reg3g knockout mouse models has been instrumental in revealing its functions in these disease-related areas, providing insights into potential treatment strategies for metabolic and liver diseases.

References:

1. Shin, Jae Hoon, Bozadjieva-Kramer, Nadejda, Shao, Yikai, Sandoval, Darleen A, Seeley, Randy J. 2022. The gut peptide Reg3g links the small intestine microbiome to the regulation of energy balance, glucose levels, and gut function. In Cell metabolism, 34, 1765-1778.e6. doi:10.1016/j.cmet.2022.09.024. https://pubmed.ncbi.nlm.nih.gov/36240758/

2. Hendrikx, Tim, Duan, Yi, Wang, Yanhan, van Pijkeren, Jan-Peter, Schnabl, Bernd. 2018. Bacteria engineered to produce IL-22 in intestine induce expression of REG3G to reduce ethanol-induced liver disease in mice. In Gut, 68, 1504-1515. doi:10.1136/gutjnl-2018-317232. https://pubmed.ncbi.nlm.nih.gov/30448775/

3. Yan, Junbin, Nie, Yunmeng, Chen, Xinli, Ding, Menglu, Zhang, Shuo. 2024. Mechanistic study of fructus aurantii (Quzhou origin) in regulating ileal reg3g in the treatment for NASH. In Phytomedicine : international journal of phytotherapy and phytopharmacology, 133, 155924. doi:10.1016/j.phymed.2024.155924. https://pubmed.ncbi.nlm.nih.gov/39098169/