(LB02-27-24) Relationship Between Metabolic Changes and Liver Health According to Prohibitin 1 Expression Level

Objectives: Prohibitin 1 (PHB1) is a mitochondrial chaperone protein acts as transcription factors and mitochondrial homeostasis. In liver cancer, PHB1 acts as a tumor suppressor. Our previous studies showed that liver specific-PHB1 deficiency induced liver injuries and increasing liver disease susceptibility against varies environment. Therefore, we predicted that Phb1 could be a key gene that protects the liver and that metabolic changes depending on Phb1 expression level would be related to the function of Phb1.

Methods: Phb1 Homozygous Knockout (HM), Phb1 Heterozygous Knockout (HT) and wild type (WT) mice were selected and sacrificed at 4 weeks of age then we collected liver and plasma specimens. Samples were analyzed using untargeted metabolomics by GC-TOF-MS. We also investigated the global gene expression gene via liver tissues RNA sequencing.

Results: We found lipid and cholesterol related genes are down regulated. Also, essential amino acids metabolism related genes and metabolites are changed. Pipecolic acid was identified as the most decreased metabolite in Phb1 HT compared to WT. Pipecolic acid is produced during the degradation of lysine. It can be produced from piperidein-6-carboxylate by pyrroline-5-carboxylate reductase (PYCR1) in lysine degradation pathway. PYCR1 is a key enzyme in proline synthesis and is identified as one of the upregulated genes in Hepatocellular carcinoma. The expression of genes involved in lysine and proline metabolism was confirmed according to the expression level of Phb1 Only changed synthesis genes of pipecolic acid and proline.

Conclusions: As a result of examining changes in genes related to mitochondrial function according to the expression level of Phb1, there was no change in Phb1 HT compared to WT. Based on these results, it was thought that Phb1 could act as a transcription factor inducing changes in lipid metabolism, lysine, and proline metabolism.

Funding Sources: This work was supported by grants provided by the National Research Foundation of Korea (NRF), funded by the Korean Government through the Ministry of Science and ICT (MSIT) (No.2020R1A2C1102451 and 2023R1A2C1007243) and by the BK21 FOUR (Fostering Out-standing Universities for Research) funded by the Ministry of Education (MOE, Korea) and NRF (NRF-5199990614253).