Martin, MatthewMotolani, AishatKim, Hyeong-GeugCollins, Amy M.Alipourgivi, FaranakJin, JiaminWei, HanWood, Barry A.Ma, Yao-YingDong, X. CharlieMirmira, Raghavendra G.Lu, Tao2024-03-222024-03-222023-09-27Martin M, Motolani A, Kim HG, et al. KDM2A Deficiency in the Liver Promotes Abnormal Liver Function and Potential Liver Damage. Biomolecules. 2023;13(10):1457. Published 2023 Sep 27. doi:10.3390/biom13101457https://hdl.handle.net/1805/39405Dysregulation of metabolic functions in the liver impacts the development of diabetes and metabolic disorders. Normal liver function can be compromised by increased inflammation via the activation of signaling such as nuclear factor (NF)-κB signaling. Notably, we have previously identified lysine demethylase 2A (KDM2A)—as a critical negative regulator of NF-κB. However, there are no studies demonstrating the effect of KDM2A on liver function. Here, we established a novel liver-specific Kdm2a knockout mouse model to evaluate KDM2A’s role in liver functions. An inducible hepatic deletion of Kdm2a, Alb-Cre-Kdm2afl/fl (Kdm2a KO), was generated by crossing the Kdm2a floxed mice (Kdm2afl/fl) we established with commercial albumin-Cre transgenic mice (B6.Cg-Tg(Alb-cre)21Mgn/J). We show that under a normal diet, Kdm2a KO mice exhibited increased serum alanine aminotransferase (ALT) activity, L-type triglycerides (TG) levels, and liver glycogen levels vs. WT (Kdm2afl/fl) animals. These changes were further enhanced in Kdm2a liver KO mice in high-fat diet (HFD) conditions. We also observed a significant increase in NF-κB target gene expression in Kdm2a liver KO mice under HFD conditions. Similarly, the KO mice exhibited increased immune cell infiltration. Collectively, these data suggest liver-specific KDM2A deficiency may enhance inflammation in the liver, potentially through NF-κB activation, and lead to liver dysfunction. Our study also suggests that the established Kdm2afl/fl mouse model may serve as a powerful tool for studying liver-related metabolic diseases.en-USAttribution 4.0 InternationalDiabetesKDM2ALiverMetabolismNF-κBArticle