Oxct1-flox Mouse

OXCT1, also known as 3-oxoacid CoA-transferase 1, is a key enzyme in ketone body metabolism. It catalyzes the first and rate-determining step of ketolysis, converting the product to acetyl-CoA which enters the tricarboxylic acid cycle for energy production [3]. OXCT1 is involved in various biological processes, such as adipogenesis, neurogenesis, and is also linked to metabolic reprogramming in cancer cells [3,4,5].

In hepatocellular carcinoma (HCC), OXCT1 has been extensively studied. In LysMcreOXCT1f/f (OXCT1 conditional knockout in macrophages) mice, inhibiting OXCT1 expression in tumor-associated macrophages reduced CD8+ T-cell exhaustion through the succinate-H3K4me3-Arg1 axis, suppressing tumor growth by reprogramming TAMs toward an antitumor phenotype [1]. In another study, in HCC cells, SUCLA2-mediated OXCT1 succinylation and activation enhanced ketolysis, cell proliferation, and tumor growth in mice, and an OXCT1 inhibitor could suppress liver tumor growth [2]. In pancreatic ductal adenocarcinoma, down-regulation of OXCT1 in cell lines increased apoptosis after gemcitabine treatment, and overexpression of OXCT1 in mouse models reduced the tumor-growth-inhibitory effect of gemcitabine, suggesting OXCT1 promotes gemcitabine resistance via the NF-κB signaling pathway [6].

In conclusion, OXCT1 is essential for ketone body metabolism and plays significant roles in multiple biological processes and diseases. The use of gene knockout and conditional knockout mouse models, such as in HCC and pancreatic cancer studies, has revealed its functions in tumor-related processes, providing potential therapeutic targets for these diseases.