Nicotinamide-N-methyltransferase regulates lipid metabolism via SAM and 1-methylnicotinamide in the AML12 hepatocyte cell line
| العنوان: | Nicotinamide-N-methyltransferase regulates lipid metabolism via SAM and 1-methylnicotinamide in the AML12 hepatocyte cell line |
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| المؤلفون: | Mayuko Yoda, Rin Mizuno, Yoshihiro Izumi, Masatomo Takahashi, Takeshi Bamba, Shinpei Kawaoka |
| المصدر: | The Journal of Biochemistry. |
| بيانات النشر: | Oxford University Press (OUP), 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | General Medicine, Molecular Biology, Biochemistry |
| الوصف: | Nicotinamide-N-methyltransferase (NNMT) is an enzyme that consumes S-adenosyl-methionine (SAM) and nicotinamide (NAM) to produce S-adenosyl-homocysteine (SAH) and 1-methylnicotinamide (MNAM). How much NNMT contributes to the quantity regulation of these four metabolites depends on whether NNMT is a major consumer or producer of these metabolites, which varies among various cellular contexts. Yet, whether NNMT critically regulates these metabolites in the AML12 hepatocyte cell line has been unexplored. To address this, we knockdown Nnmt in AML12 cells and investigate the effects of Nnmt RNAi on metabolism and gene expression. We find that Nnmt RNAi accumulates SAM and SAH, whereas it reduces MNAM with NAM being unaltered. These results indicate that NNMT is a significant consumer of SAM and critical for MNAM production in this cell line. Moreover, transcriptome analyses reveal that altered SAM and MNAM homeostasis is accompanied by various detrimental molecular phenotypes, as exemplified by the down-regulations of lipogenic genes, such as Srebf1. Consistent with this, oil-red O-staining experiments demonstrate the decrease of total neutral lipids upon Nnmt RNAi. Treating Nnmt RNAi AML12 cells with cycloleucine, an inhibitor of SAM biogenesis suppresses SAM accumulation and rescues the decrease of neutral lipids. MNAM also shows activity to elevate neutral lipids. These results suggest that NNMT contributes to lipid metabolism by maintaining proper SAM and MNAM homeostasis. This study provides an additional example where NNMT plays a critical role in regulating SAM and MNAM metabolism. |
| تدمد: | 1756-2651 0021-924X |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::ecb40d4ef29de734e408fdb5ff821822Test https://doi.org/10.1093/jb/mvad028Test |
| حقوق: | EMBARGO |
| رقم الانضمام: | edsair.doi...........ecb40d4ef29de734e408fdb5ff821822 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17562651 0021924X |
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