Reg3g, also known as regenerating islet-derived 3 gamma, is an antimicrobial peptide. It has crucial functions in linking the small intestine microbiome to host physiology, regulating energy balance, glucose levels, and gut function. It may act within the lumen and as a gut hormone. Also, it is involved in innate immunity and has been associated with the IL-22 signaling pathway [1,2].

In Reg3g knockout mice, beneficial effects of high-inulin diets and vertical sleeve gastrectomy on gut function, energy balance, and glucose regulation are absent, suggesting its essential role in these processes [1]. Additionally, in alcoholic liver disease, reduced REG3G expression due to ethanol-induced dysbiosis leads to bacterial translocation to the liver and steatohepatitis, and engineered bacteria inducing REG3G expression can reduce this liver disease [2]. In non-alcoholic steatohepatitis (NASH), decreased expression of reg3g is associated with disease progression, and Fructus Aurantii can ameliorate NASH by upregulating reg3g, which helps repair the intestinal barrier and reduce endotoxin-related inflammation and fibrosis [3].

In conclusion, Reg3g is vital in maintaining normal physiological functions related to metabolism, gut-liver axis, and innate immunity. The use of Reg3g knockout mouse models has revealed its significance in diseases such as obesity-related metabolic disorders, alcoholic liver disease, and NASH, providing insights into potential treatment strategies for these conditions.