Pokemon, a transcriptional repressor, inhibits the transcription of tumor suppressor genes and promotes tumor formation by affecting chromatin recombination or binding directly to the tumor suppressor genes. In this study, the mechanism behind the Pokemon regulation of liver cancer cell metabolism was evaluated using liquid chromatography-mass spectrometry (LC-MS)-based metabolomics. Pokemon-overexpressing HL7702 cells were obtained by lipofection. The cells were collected at different time points after transfection and their intracellular metabolites were analyzed using an LC-MS-based metabolomic method. Based on the results of a multivariate statistical analysis, candidate metabolites with significant differences were selected, and 36 of them were confirmed by database and MS/MS analysis. These metabolites were primarily involved in lipid synthesis by KEGG database searches. Further analysis indicated that both the acetyl-coenzyme carboxylase and the fatty acid synthase were activated in the lipid synthesis pathway. The results show that Pokemon can affect cell metabolism by activating the lipid synthesis pathways in cells.

Medium-chain fatty acids (MCFA) are dietary components with a chain length ranging from 6 to 12 carbon atoms. MCFA can cross the blood-brain barrier and in the brain can be oxidized through mitochondrial β-oxidation. As components of ketogenic diets, MCFA have demonstrated beneficial effects on different brain diseases, such as traumatic brain injury, Alzheimer\'s disease, drug-resistant epilepsy, diabetes, and cancer. Despite the interest in MCFA effects, not much information is available about MCFA metabolism in the brain. In this study, with a gas chromatography-mass spectrometry (GC-MS)-based metabolomics approach, coupled with multivariate data analyses, we followed the metabolic changes of U87MG glioblastoma cells after the addition of octanoic (C8), or decanoic (C10) acids for 24 h. Our analysis highlighted significant differences in the metabolism of U87MG cells after the addition of C8 or C10 and identified several metabolites whose amount changed between the two groups of treated cells. Overall, metabolic pathway analyses suggested the citric acid cycle, Warburg effect, glutamine/glutamate metabolism, and ketone body metabolism as pathways influenced by C8 or C10 addition to U87MG cells. Our data demonstrated that, while C8 affected mitochondrial metabolism resulting in increased ketone body production, C10 mainly influenced cytosolic pathways by stimulating fatty acid synthesis. Moreover, glutamine might be the main substrate to support fatty acids synthesis in C10-treated cells. In conclusion, we identified a metabolic signature associated with C8 or C10 addition to U87MG cells that can be used to decipher metabolic responses of glioblastoma cells to MCFA treatment.