(P20-029-25) Effect of S-adenosylmethionine on Lipid Metabolism Through ER Stress Regulation in Hepatocytes

Objectives: Lipid metabolism in the liver plays an important role in the development and progression of liver disease. ER is an organelle that plays an important role in intracellular lipid metabolism, and when ER stress occurs, abnormal lipid metabolism occurs. S-adenosylmethionine (SAMe) is a metabolite of methionine and is known to have various functions including antioxidant properties. In this study, we aimed to determine whether SAMe could affect lipid metabolism by helping to alleviate ER stress in the liver.

Methods: The cell line used in the experiment was HepG2, a human hepatocarcinoma cell. After cell seeding, 0.5mM of SAMe was treated for 24 hours. ER stress was induced with 1 μg/mL of tunicamycin (TM) and 750 μM of palmitic acid (PA) was treated to confirm lipid metabolism.

Results: As a result, treatment with PA increased the expression of ER stress markers and when TM and PA were treated together, ER stress markers such as CHOP and eIF2a, as well as GRP78, ATF4, and PERK1, increased more than the group treated with PA alone. In addition, SAMe increased the mRNA expression of PPARγ, which regulates lipid metabolism, and the expression of other genes related to fat metabolism also showed a tendency to increase. In the group treated with PA, the expression of CPT1a increased, but in the group treated with TM and PA together, the expression did not increase. However, when TM and PA were treated together in the SAMe-treated group, the mRNA expression level of CPT1a was increased.

Conclusions: Through the above experimental results, it was confirmed that although is believed to have the potential to alleviate ER stress caused by PA through decreasing the expression of ER stress markers increased by PA. In addition, SAMe appears to be able to effectively eliminate lipid metabolism-derived ER stress by increasing the expression of lipid metabolism regulators such as PPARγ. In summary, SAMe can be expected to reduce intracellular stress caused by lipid metabolism through regulating ER stress in hepatocytes.

Funding Sources: This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (Ministry of Science and ICT) (No. (RS-2020-NR048515 and RS-2023-NR076861) and BK21 FOUR (Fostering Outstanding Universities for Research) funded by the Ministry of Education (MOE, Korea) and National Research Foundation of Korea (NRF-5199990614253).