دورية أكاديمية
Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression
| العنوان: | Spermidine-mediated hypusination of translation factor EIF5A improves mitochondrial fatty acid oxidation and prevents non-alcoholic steatohepatitis progression |
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| المؤلفون: | Zhou, J, Pang, J, Tripathi, M, Ho, JP, Widjaja, AA, Shekeran, SG, Cook, SA, Suzuki, A, Diehl, AM, Petretto, E, Singh, BK, Yen, PM |
| المصدر: | 14 ; 1 |
| بيانات النشر: | Nature Research |
| سنة النشر: | 2022 |
| المجموعة: | Imperial College London: Spiral |
| مصطلحات موضوعية: | Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, LIVER-DISEASE, INSULIN-RESISTANCE, LIFE-SPAN, EF-P, PROTEIN, PROLINE, IDENTIFICATION, LIPOTOXICITY, ASSOCIATION, ADAPTATION, Animals, Fatty Acids, Lysine, Mice, Mitochondria, Non-alcoholic Fatty Liver Disease, Peptide Initiation Factors, Spermidine |
| الوصف: | Spermidine is a natural polyamine that has health benefits and extends life span in several species. Deoxyhypusine synthase (DHPS) and deoxyhypusine hydroxylase (DOHH) are key enzymes that utilize spermidine to catalyze the post-translational hypusination of the translation factor EIF5A (EIF5AH). Here, we have found that hepatic DOHH mRNA expression is decreased in patients and mice with non-alcoholic steatohepatitis (NASH), and hepatic cells treated with fatty acids. The mouse and cell culture models of NASH have concomitant decreases in Eif5aH and mitochondrial protein synthesis which leads to lower mitochondrial activity and fatty acid β-oxidation. Spermidine treatment restores EIF5AH, partially restores protein synthesis and mitochondrial function in NASH, and prevents NASH progression in vivo. Thus, the disrupted DHPS-DOHH-EIF5AH pathway during NASH represents a therapeutic target to increase hepatic protein synthesis and mitochondrial fatty acid oxidation (FAO) and prevent NASH progression. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2041-1723 |
| العلاقة: | Nature Communications; http://hdl.handle.net/10044/1/100773Test |
| DOI: | 10.1038/s41467-022-32788-x |
| الإتاحة: | https://doi.org/10.1038/s41467-022-32788-xTest http://hdl.handle.net/10044/1/100773Test |
| حقوق: | © The Author(s) 2022. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0Test/. ; http://creativecommons.org/licenses/by/4.0Test/ |
| رقم الانضمام: | edsbas.55FF9933 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 20411723 |
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| DOI: | 10.1038/s41467-022-32788-x |