Scientific reports, 2020-10, Vol.10 (1), p.18367-18367, Article 18367
2020
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- Autor(en) / Beteiligte
- Titel
- Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice
- Ist Teil von
- Scientific reports, 2020-10, Vol.10 (1), p.18367-18367, Article 18367
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2020
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Medium-chain triglycerides (MCT), containing C -C fatty acids, are used to treat several pediatric disorders and are widely consumed as a nutritional supplement. Here, we investigated the role of the sirtuin deacylase Sirt5 in MCT metabolism by feeding Sirt5 knockout mice (Sirt5KO) high-fat diets containing either C /C fatty acids or coconut oil, which is rich in C , for five weeks. Coconut oil, but not C /C feeding, induced periportal macrovesicular steatosis in Sirt5KO mice. C-C degradation was significantly reduced in Sirt5KO liver. This decrease was localized to the mitochondrial β-oxidation pathway, as Sirt5KO mice exhibited no change in peroxisomal C β-oxidation. Endoplasmic reticulum ω-oxidation, a minor fatty acid degradation pathway known to be stimulated by C accumulation, was increased in Sirt5KO liver. Mice lacking another mitochondrial C oxidation enzyme, long-chain acyl-CoA dehydrogenase (LCAD), also developed periportal macrovesicular steatosis when fed coconut oil, confirming that defective mitochondrial C oxidation is sufficient to induce the steatosis phenotype. Sirt5KO liver exhibited normal LCAD activity but reduced mitochondrial acyl-CoA synthetase activity with C . These studies reveal a role for Sirt5 in regulating the hepatic response to MCT and may shed light into the pathogenesis of periportal steatosis, a hallmark of human pediatric non-alcoholic fatty liver disease.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 2045-2322eISSN: 2045-2322DOI: 10.1038/s41598-020-75615-3Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7591893
- Format
- –
- Schlagworte
- Acyl-CoA dehydrogenase, Acyl-CoA Dehydrogenase, Long-Chain - metabolism, Animals, Coconut oil, Coconut Oil - administration & dosage, Dietary Fats - administration & dosage, Endoplasmic reticulum, Fatty acids, Fatty Acids - metabolism, Fatty liver, Female, High fat diet, Liver, Liver diseases, Male, Mice, Mice, Knockout, Mitochondria, Mitochondria, Liver - metabolism, Non-alcoholic Fatty Liver Disease - genetics, Non-alcoholic Fatty Liver Disease - metabolism, Oxidation, Oxidation-Reduction, Pediatrics, Phenotypes, Sirtuins - genetics, Steatosis, Triglycerides, Triglycerides - metabolism