Zbtb22, Zinc Finger And BTB Domain Containing 22, is associated with multiple biological processes. It has been found in the genomic regions related to major histocompatibility complex in some species [3,4]. In the liver, it plays a role in metabolic and detoxification-related pathways, which are crucial for maintaining normal physiological functions [1,2]. Genetic models, such as KO mouse models, are valuable for studying its functions.

In the context of diabetes, hepatic Zbtb22 overexpression increases gluconeogenic and lipogenic gene expression, leading to hyperglycemia, insulin resistance, and increased lipid accumulation. Conversely, Zbtb22-deficient mice display improved energy expenditure, glucose tolerance, and insulin sensitivity, along with reduced hepatic steatosis. Zbtb22 directly binds to the promoter region of PCK1 to enhance its expression and increase gluconeogenesis. Silencing PCK1 abolishes the effects of Zbtb22 overexpression on glucose and lipid metabolism [1]. Regarding acetaminophen-induced liver injury, hepatic Zbtb22 expression is reduced in affected patients and mice. Zbtb22 deletion in mouse primary hepatocytes aggravates the injury, while overexpression attenuates it. Zbtb22 decreases pregnane X receptor (PXR) expression, and the PXR activator suppresses the protective effect of Zbtb22 [2].

In conclusion, Zbtb22 is involved in liver-related metabolic and detoxification processes. The use of Zbtb22 KO mouse models has revealed its role in diabetes-related metabolic disorders and acetaminophen-induced liver injury, providing potential therapeutic targets for these disease areas.