SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside
| العنوان: | SIRT3 is required for liver regeneration but not for the beneficial effect of nicotinamide riboside |
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| المؤلفون: | Jade Toth, Sarmistha Mukherjee, Karthikeyani Chellappa, Qingwei Chu, James Mo, Caroline Perry, Lauren M Paolella, Joseph A. Baur, Mindy M Hugo, Qiang Tong |
| المصدر: | JCI Insight JCI Insight, Vol 6, Iss 7 (2021) |
| بيانات النشر: | American Society for Clinical Investigation, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Niacinamide, SIRT3, Mice, Transgenic, Mitochondria, Liver, Pyridinium Compounds, Mitochondrion, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Sirtuin 1, Sirtuin 3, Animals, Beta oxidation, Molecular pathology, Mice, Knockout, biology, Hepatology, Regeneration (biology), General Medicine, Liver regeneration, Cell biology, Mitochondria, Liver Regeneration, Mice, Inbred C57BL, 030104 developmental biology, Metabolism, chemistry, 030220 oncology & carcinogenesis, Fatty acid oxidation, Sirtuin, Nicotinamide riboside, biology.protein, Hepatocytes, Medicine, NAD+ kinase, Oxidation-Reduction, Research Article |
| الوصف: | Liver regeneration is critical to survival after traumatic injuries, exposure to hepatotoxins, or surgical interventions, yet the underlying signaling and metabolic pathways remain unclear. In this study, we show that hepatocyte-specific loss of the mitochondrial deacetylase SIRT3 drastically impairs regeneration and worsens mitochondrial function after partial hepatectomy. Sirtuins, including SIRT3, require NAD as a cosubstrate. We previously showed that the NAD precursor nicotinamide riboside (NR) promotes liver regeneration, but whether this involves sirtuins has not been tested. Here, we show that despite their NAD dependence and critical roles in regeneration, neither SIRT3 nor its nuclear counterpart SIRT1 is required for NR to enhance liver regeneration. NR improves mitochondrial respiration in regenerating WT or mutant livers and rapidly increases oxygen consumption and glucose output in cultured hepatocytes. Our data support a direct enhancement of mitochondrial redox metabolism as the mechanism mediating improved liver regeneration after NAD supplementation and exclude signaling via SIRT1 and SIRT3. Therefore, we provide the first evidence to our knowledge for an essential role for a mitochondrial sirtuin during liver regeneration and insight into the beneficial effects of NR. |
| اللغة: | English |
| تدمد: | 2379-3708 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cb125375f2ac8d6e3ece0d2fc49fc050Test http://europepmc.org/articles/PMC8119200Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....cb125375f2ac8d6e3ece0d2fc49fc050 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23793708 |
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