{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T10:56:25Z","timestamp":1792234585165,"version":"4.4.0"},"reference-count":55,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T00:00:00Z","timestamp":1603756800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["090242"],"award-info":[{"award-number":["090242"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"crossref","award":["090242"],"award-info":[{"award-number":["090242"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Medium-chain triglycerides (MCT), containing C<jats:sub>8<\/jats:sub>\u2013C<jats:sub>12<\/jats:sub> 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<jats:sub>8<\/jats:sub>\/C<jats:sub>10<\/jats:sub> fatty acids or coconut oil, which is rich in C<jats:sub>12<\/jats:sub>, for five weeks. Coconut oil, but not C<jats:sub>8<\/jats:sub>\/C<jats:sub>10<\/jats:sub> feeding, induced periportal macrovesicular steatosis in Sirt5KO mice. <jats:sup>14<\/jats:sup>C\u2013C<jats:sub>12<\/jats:sub> degradation was significantly reduced in Sirt5KO liver. This decrease was localized to the mitochondrial \u03b2-oxidation pathway, as Sirt5KO mice exhibited no change in peroxisomal C<jats:sub>12<\/jats:sub> \u03b2-oxidation. Endoplasmic reticulum \u03c9-oxidation, a minor fatty acid degradation pathway known to be stimulated by C<jats:sub>12<\/jats:sub> accumulation, was increased in Sirt5KO liver. Mice lacking another mitochondrial C<jats:sub>12<\/jats:sub> oxidation enzyme, long-chain acyl-CoA dehydrogenase (LCAD), also developed periportal macrovesicular steatosis when fed coconut oil, confirming that defective mitochondrial C<jats:sub>12<\/jats:sub> oxidation is sufficient to induce the steatosis phenotype. Sirt5KO liver exhibited normal LCAD activity but reduced mitochondrial acyl-CoA synthetase activity with C<jats:sub>12<\/jats:sub>. 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.<\/jats:p>","DOI":"10.1038\/s41598-020-75615-3","type":"journal-article","created":{"date-parts":[[2020,10,27]],"date-time":"2020-10-27T11:03:40Z","timestamp":1603796620000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Impaired mitochondrial medium-chain fatty acid oxidation drives periportal macrovesicular steatosis in sirtuin-5 knockout mice"],"prefix":"10.1038","volume":"10","author":[{"given":"Eric S.","family":"Goetzman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sivakama S.","family":"Bharathi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Jun","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven F.","family":"Dobrowolski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Peasley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunder","family":"Sims-Lucas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satdarshan P.","family":"Monga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,10,27]]},"reference":[{"key":"75615_CR1","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1016\/j.molcel.2015.05.022","volume":"59","author":"Y Nishida","year":"2015","unstructured":"Nishida, Y. et al. SIRT5 regulates both cytosolic and mitochondrial protein malonylation with glycolysis as a major target. Mol. Cell 59, 321\u2013332. https:\/\/doi.org\/10.1016\/j.molcel.2015.05.022 (2015).","journal-title":"Mol. Cell"},{"key":"75615_CR2","doi-asserted-by":"publisher","first-page":"605","DOI":"10.1016\/j.cmet.2014.03.014","volume":"19","author":"M Tan","year":"2014","unstructured":"Tan, M. et al. Lysine glutarylation is a protein posttranslational modification regulated by SIRT5. Cell Metab. 19, 605\u2013617. https:\/\/doi.org\/10.1016\/j.cmet.2014.03.014 (2014).","journal-title":"Cell Metab."},{"key":"75615_CR3","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1016\/j.cmet.2013.11.013","volume":"18","author":"MJ Rardin","year":"2013","unstructured":"Rardin, M. J. et al. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. Cell Metab. 18, 920\u2013933. https:\/\/doi.org\/10.1016\/j.cmet.2013.11.013 (2013).","journal-title":"Cell Metab."},{"key":"75615_CR4","doi-asserted-by":"publisher","unstructured":"Chen, X. F. et al. SIRT5 inhibits peroxisomal ACOX1 to prevent oxidative damage and is downregulated in liver cancer. EMBO Rep. 19, https:\/\/doi.org\/10.15252\/embr.201745124 (2018).","DOI":"10.15252\/embr.201745124"},{"key":"75615_CR5","doi-asserted-by":"publisher","first-page":"e0122297","DOI":"10.1371\/journal.pone.0122297","volume":"10","author":"Y Zhang","year":"2015","unstructured":"Zhang, Y. et al. SIRT3 and SIRT5 regulate the enzyme activity and cardiolipin binding of very long-chain acyl-CoA dehydrogenase. PLoS ONE 10, e0122297. https:\/\/doi.org\/10.1371\/journal.pone.0122297 (2015).","journal-title":"PLoS ONE"},{"key":"75615_CR6","doi-asserted-by":"publisher","unstructured":"Kapoor, V., Malviya, M. N. & Soll, R. Lipid emulsions for parenterally fed term and late preterm infants. Cochrane Database Syst. Rev. 6, CD013171, https:\/\/doi.org\/10.1002\/14651858.CD013171.pub2 (2019).","DOI":"10.1002\/14651858.CD013171.pub2"},{"key":"75615_CR7","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s10545-017-0085-8","volume":"40","author":"MB Gillingham","year":"2017","unstructured":"Gillingham, M. B. et al. Triheptanoin versus trioctanoin for long-chain fatty acid oxidation disorders: A double blinded, randomized controlled trial. J. Inherit. Metab. Dis. 40, 831\u2013843. https:\/\/doi.org\/10.1007\/s10545-017-0085-8 (2017).","journal-title":"J. Inherit. Metab. Dis."},{"key":"75615_CR8","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1002\/epi4.12308","volume":"4","author":"K Borges","year":"2019","unstructured":"Borges, K., Kaul, N., Germaine, J., Kwan, P. & O\u2019Brien, T. J. Randomized trial of add-on triheptanoin vs medium chain triglycerides in adults with refractory epilepsy. Epilepsia Open 4, 153\u2013163. https:\/\/doi.org\/10.1002\/epi4.12308 (2019).","journal-title":"Epilepsia Open"},{"key":"75615_CR9","first-page":"20","volume":"160","author":"ND Shah","year":"2017","unstructured":"Shah, N. D. & Limketkai, B. N. The use of medium-chain triglycerides in gastrointestinal disorders. Pract. Gastroenterol. 160, 20\u201328 (2017).","journal-title":"Pract. Gastroenterol."},{"key":"75615_CR10","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1007\/s13668-018-0230-5","volume":"7","author":"S Sankararaman","year":"2018","unstructured":"Sankararaman, S. & Sferra, T. J. Are we going nuts on coconut oil?. Curr. Nutr. Rep. 7, 107\u2013115. https:\/\/doi.org\/10.1007\/s13668-018-0230-5 (2018).","journal-title":"Curr. Nutr. Rep."},{"key":"75615_CR11","doi-asserted-by":"publisher","first-page":"46","DOI":"10.3389\/fnut.2019.00046","volume":"6","author":"V St-Pierre","year":"2019","unstructured":"St-Pierre, V. et al. Plasma ketone and medium chain fatty acid response in humans consuming different medium chain triglycerides during a metabolic study day. Front. Nutr. 6, 46. https:\/\/doi.org\/10.3389\/fnut.2019.00046 (2019).","journal-title":"Front. Nutr."},{"key":"75615_CR12","doi-asserted-by":"crossref","first-page":"189","DOI":"10.4314\/gmj.v50i3.11","volume":"50","author":"L Boateng","year":"2016","unstructured":"Boateng, L., Ansong, R., Owusu, W. B. & Steiner-Asiedu, M. Coconut oil and palm oil\u2019s role in nutrition, health and national development: A review. Ghana Med. J. 50, 189\u2013196 (2016).","journal-title":"Ghana Med. J."},{"key":"75615_CR13","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1016\/s0304-4165(99)00088-4","volume":"1428","author":"DA Vessey","year":"1999","unstructured":"Vessey, D. A., Kelley, M. & Warren, R. S. Characterization of the CoA ligases of human liver mitochondria catalyzing the activation of short- and medium-chain fatty acids and xenobiotic carboxylic acids. Biochim. Biophys. Acta 1428, 455\u2013462. https:\/\/doi.org\/10.1016\/s0304-4165(99)00088-4 (1999).","journal-title":"Biochim. Biophys. Acta"},{"key":"75615_CR14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1146\/annurev-nutr-071813-105541","volume":"34","author":"TJ Grevengoed","year":"2014","unstructured":"Grevengoed, T. J., Klett, E. L. & Coleman, R. A. Acyl-CoA metabolism and partitioning. Annu. Rev. Nutr. 34, 1\u201330. https:\/\/doi.org\/10.1146\/annurev-nutr-071813-105541 (2014).","journal-title":"Annu. Rev. Nutr."},{"key":"75615_CR15","doi-asserted-by":"publisher","first-page":"299","DOI":"10.1017\/S0007114599001506","volume":"82","author":"C Piot","year":"1999","unstructured":"Piot, C., Hocquette, J. F., Veerkamp, J. H., Durand, D. & Bauchart, D. Effects of dietary coconut oil on fatty acid oxidation capacity of the liver, the heart and skeletal muscles in the preruminant calf. Br. J. Nutr. 82, 299\u2013308 (1999).","journal-title":"Br. J. Nutr."},{"key":"75615_CR16","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/0005-2760(91)90022-A","volume":"1081","author":"E Christensen","year":"1991","unstructured":"Christensen, E., Gronn, M., Hagve, T. A. & Christophersen, B. O. Omega-oxidation of fatty acids studied in isolated liver cells. Biochim. Biophys. Acta 1081, 167\u2013173 (1991).","journal-title":"Biochim. Biophys. Acta"},{"key":"75615_CR17","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1002\/humu.20535","volume":"28","author":"S Ferdinandusse","year":"2007","unstructured":"Ferdinandusse, S. et al. Clinical, biochemical, and mutational spectrum of peroxisomal acyl-coenzyme A oxidase deficiency. Hum. Mutat. 28, 904\u2013912. https:\/\/doi.org\/10.1002\/humu.20535 (2007).","journal-title":"Hum. Mutat."},{"key":"75615_CR18","doi-asserted-by":"crossref","unstructured":"18Tserng, K. Y. & Jin, S. J. Metabolic conversion of dicarboxylic acids to succinate in rat liver homogenates. A stable isotope tracer study. J. Biol. Chem. 266, 2924\u20132929 (1991).","DOI":"10.1016\/S0021-9258(18)49936-X"},{"key":"75615_CR19","doi-asserted-by":"publisher","first-page":"2736","DOI":"10.1194\/jlr.M700378-JLR200","volume":"48","author":"PA Watkins","year":"2007","unstructured":"Watkins, P. A., Maiguel, D., Jia, Z. & Pevsner, J. Evidence for 26 distinct acyl-coenzyme A synthetase genes in the human genome. J. Lipid Res. 48, 2736\u20132750. https:\/\/doi.org\/10.1194\/jlr.M700378-JLR200 (2007).","journal-title":"J. Lipid Res."},{"key":"75615_CR20","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ymgme.2010.05.005","volume":"101","author":"S Tucci","year":"2010","unstructured":"Tucci, S., Primassin, S., Ter Veld, F. & Spiekerkoetter, U. Medium-chain triglycerides impair lipid metabolism and induce hepatic steatosis in very long-chain acyl-CoA dehydrogenase (VLCAD)-deficient mice. Mol. Genet. Metab. 101, 40\u201347. https:\/\/doi.org\/10.1016\/j.ymgme.2010.05.005 (2010).","journal-title":"Mol. Genet. Metab."},{"key":"75615_CR21","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1002\/jsfa.8650","volume":"98","author":"A Narayanankutty","year":"2018","unstructured":"Narayanankutty, A., Palliyil, D. M., Kuruvilla, K. & Raghavamenon, A. C. Virgin coconut oil reverses hepatic steatosis by restoring redox homeostasis and lipid metabolism in male Wistar rats. J. Sci. Food Agric. 98, 1757\u20131764. https:\/\/doi.org\/10.1002\/jsfa.8650 (2018).","journal-title":"J. Sci. Food Agric."},{"key":"75615_CR22","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1007\/s11130-017-0643-0","volume":"72","author":"SK Panchal","year":"2017","unstructured":"Panchal, S. K., Carnahan, S. & Brown, L. Coconut products improve signs of diet-induced metabolic syndrome in rats. Plant Foods Hum. Nutr. 72, 418\u2013424. https:\/\/doi.org\/10.1007\/s11130-017-0643-0 (2017).","journal-title":"Plant Foods Hum. Nutr."},{"key":"75615_CR23","doi-asserted-by":"publisher","unstructured":"Africa, J. A. et al. In children with nonalcoholic fatty liver disease, zone 1 steatosis is associated with advanced fibrosis. Clin. Gastroenterol. Hepatol. 16, 438\u2013446 e431, https:\/\/doi.org\/10.1016\/j.cgh.2017.02.030 (2018).","DOI":"10.1016\/j.cgh.2017.02.030"},{"key":"75615_CR24","doi-asserted-by":"publisher","first-page":"24156","DOI":"10.1038\/srep24156","volume":"6","author":"L Li","year":"2016","unstructured":"Li, L. et al. PGC-1alpha promotes ureagenesis in mouse periportal hepatocytes through SIRT3 and SIRT5 in response to glucagon. Sci. Rep. 6, 24156. https:\/\/doi.org\/10.1038\/srep24156 (2016).","journal-title":"Sci. Rep."},{"key":"75615_CR25","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1016\/j.bbrc.2007.06.059","volume":"360","author":"D Oaxaca-Castillo","year":"2007","unstructured":"Oaxaca-Castillo, D. et al. Biochemical characterization of two functional human liver acyl-CoA oxidase isoforms 1a and 1b encoded by a single gene. Biochem. Biophys. Res. Commun. 360, 314\u2013319. https:\/\/doi.org\/10.1016\/j.bbrc.2007.06.059 (2007).","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"75615_CR26","doi-asserted-by":"publisher","unstructured":"Mortensen, P. B. & Gregersen, N. The biological origin of ketotic dicarboxylic aciduria. In vivo and in vitro investigations of the omega-oxidation of C6\u2013C16-monocarboxylic acids in unstarved, starved and diabetic rats. Biochim. Biophys. Acta 666, 394\u2013404, https:\/\/doi.org\/10.1016\/0005-2760(81)90298-8 (1981).","DOI":"10.1016\/0005-2760(81)90298-8"},{"key":"75615_CR27","doi-asserted-by":"publisher","first-page":"248","DOI":"10.1016\/j.celrep.2013.08.032","volume":"5","author":"J Ding","year":"2013","unstructured":"Ding, J. et al. The peroxisomal enzyme L-PBE is required to prevent the dietary toxicity of medium-chain fatty acids. Cell Rep. 5, 248\u2013258. https:\/\/doi.org\/10.1016\/j.celrep.2013.08.032 (2013).","journal-title":"Cell Rep."},{"key":"75615_CR28","doi-asserted-by":"publisher","unstructured":"Wanders, R. J., Ruiter, J. P., L, I. J., Waterham, H. R. & Houten, S. M. The enzymology of mitochondrial fatty acid beta-oxidation and its application to follow-up analysis of positive neonatal screening results. J. Inherit. Metab. Dis. 33, 479\u2013494, https:\/\/doi.org\/10.1007\/s10545-010-9104-8 (2010).","DOI":"10.1007\/s10545-010-9104-8"},{"key":"75615_CR29","doi-asserted-by":"publisher","unstructured":"Wanders, R. J., Denis, S., Ruiter, J. P., L, I. J. & Dacremont, G. 2,6-Dimethylheptanoyl-CoA is a specific substrate for long-chain acyl-CoA dehydrogenase (LCAD): Evidence for a major role of LCAD in branched-chain fatty acid oxidation. Biochim. Biophys. Acta 1393, 35\u201340, https:\/\/doi.org\/10.1016\/s0005-2760(98)00053-8 (1998).","DOI":"10.1016\/s0005-2760(98)00053-8"},{"key":"75615_CR30","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1203\/00006450-199707000-00017","volume":"42","author":"T Nakajima","year":"1997","unstructured":"Nakajima, T. et al. The effect of carnitine on ketogenesis in perfused livers from juvenile visceral steatosis mice with systemic carnitine deficiency. Pediatr. Res. 42, 108\u2013113. https:\/\/doi.org\/10.1203\/00006450-199707000-00017 (1997).","journal-title":"Pediatr. Res."},{"key":"75615_CR31","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1152\/physrev.1983.63.4.1420","volume":"63","author":"J Bremer","year":"1983","unstructured":"Bremer, J. Carnitine\u2014Metabolism and functions. Physiol. Rev. 63, 1420\u20131480. https:\/\/doi.org\/10.1152\/physrev.1983.63.4.1420 (1983).","journal-title":"Physiol. Rev."},{"key":"75615_CR32","doi-asserted-by":"publisher","first-page":"2244","DOI":"10.1172\/JCI119034","volume":"98","author":"LS Sidossis","year":"1996","unstructured":"Sidossis, L. S., Stuart, C. A., Shulman, G. I., Lopaschuk, G. D. & Wolfe, R. R. Glucose plus insulin regulate fat oxidation by controlling the rate of fatty acid entry into the mitochondria. J. Clin. Investig. 98, 2244\u20132250. https:\/\/doi.org\/10.1172\/JCI119034 (1996).","journal-title":"J. Clin. Investig."},{"key":"75615_CR33","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1111\/j.1432-1033.1996.0186r.x","volume":"242","author":"H Iijima","year":"1996","unstructured":"Iijima, H. et al. Biochemical studies of two rat acyl-CoA synthetases, ACS1 and ACS2. Eur. J. Biochem. 242, 186\u2013190. https:\/\/doi.org\/10.1111\/j.1432-1033.1996.0186r.x (1996).","journal-title":"Eur. J. Biochem."},{"key":"75615_CR34","doi-asserted-by":"publisher","first-page":"16748","DOI":"10.1074\/jbc.271.28.16748","volume":"271","author":"T Fujino","year":"1996","unstructured":"Fujino, T., Kang, M. J., Suzuki, H., Iijima, H. & Yamamoto, T. Molecular characterization and expression of rat acyl-CoA synthetase 3. J. Biol. Chem. 271, 16748\u201316752. https:\/\/doi.org\/10.1074\/jbc.271.28.16748 (1996).","journal-title":"J. Biol. Chem."},{"key":"75615_CR35","doi-asserted-by":"publisher","first-page":"10239","DOI":"10.1074\/jbc.M117.785022","volume":"292","author":"Y Zhang","year":"2017","unstructured":"Zhang, Y. et al. Lysine desuccinylase SIRT5 binds to cardiolipin and regulates the electron transport chain. J. Biol. Chem. 292, 10239\u201310249. https:\/\/doi.org\/10.1074\/jbc.M117.785022 (2017).","journal-title":"J. Biol. Chem."},{"issue":"Pt 3","key":"75615_CR36","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1042\/bj3110853","volume":"311","author":"M Guzman","year":"1995","unstructured":"Guzman, M., Bijleveld, C. & Geelen, M. J. Flexibility of zonation of fatty acid oxidation in rat liver. Biochem. J. 311(Pt 3), 853\u2013860. https:\/\/doi.org\/10.1042\/bj3110853 (1995).","journal-title":"Biochem. J."},{"key":"75615_CR37","doi-asserted-by":"publisher","first-page":"1219","DOI":"10.1177\/002215549904701001","volume":"47","author":"HD Fahimi","year":"1999","unstructured":"Fahimi, H. D. & Baumgart, E. Current cytochemical techniques for the investigation of peroxisomes. A review. J. Histochem. Cytochem. 47, 1219\u20131232. https:\/\/doi.org\/10.1177\/002215549904701001 (1999).","journal-title":"J. Histochem. Cytochem."},{"key":"75615_CR38","doi-asserted-by":"publisher","first-page":"354","DOI":"10.1016\/j.molmet.2014.02.002","volume":"3","author":"S Kersten","year":"2014","unstructured":"Kersten, S. Integrated physiology and systems biology of PPARalpha. Mol. Metab. 3, 354\u2013371. https:\/\/doi.org\/10.1016\/j.molmet.2014.02.002 (2014).","journal-title":"Mol. Metab."},{"key":"75615_CR39","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.biochi.2013.09.019","volume":"98","author":"J Vamecq","year":"2014","unstructured":"Vamecq, J., Cherkaoui-Malki, M., Andreoletti, P. & Latruffe, N. The human peroxisome in health and disease: The story of an oddity becoming a vital organelle. Biochimie 98, 4\u201315. https:\/\/doi.org\/10.1016\/j.biochi.2013.09.019 (2014).","journal-title":"Biochimie"},{"key":"75615_CR40","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1002\/jimd.12083","volume":"43","author":"M Schrader","year":"2020","unstructured":"Schrader, M., Kamoshita, M. & Islinger, M. Organelle interplay-peroxisome interactions in health and disease. J. Inherit. Metab. Dis. 43, 71\u201389. https:\/\/doi.org\/10.1002\/jimd.12083 (2020).","journal-title":"J. Inherit. Metab. Dis."},{"key":"75615_CR41","doi-asserted-by":"publisher","first-page":"2940","DOI":"10.1038\/s41467-018-05277-3","volume":"9","author":"AS Joshi","year":"2018","unstructured":"Joshi, A. S. et al. Lipid droplet and peroxisome biogenesis occur at the same ER subdomains. Nat. Commun. 9, 2940. https:\/\/doi.org\/10.1038\/s41467-018-05277-3 (2018).","journal-title":"Nat. Commun."},{"key":"75615_CR42","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1074\/jbc.M111.272732","volume":"287","author":"M Hillebrand","year":"2012","unstructured":"Hillebrand, M. et al. Identification of a new fatty acid synthesis-transport machinery at the peroxisomal membrane. J. Biol. Chem. 287, 210\u2013221. https:\/\/doi.org\/10.1074\/jbc.M111.272732 (2012).","journal-title":"J. Biol. Chem."},{"key":"75615_CR43","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1042\/BJ20050144","volume":"389","author":"T Kasumov","year":"2005","unstructured":"Kasumov, T. et al. Probing peroxisomal beta-oxidation and the labelling of acetyl-CoA proxies with [1-(13C)]octanoate and [3-(13C)]octanoate in the perfused rat liver. Biochem. J. 389, 397\u2013401. https:\/\/doi.org\/10.1042\/BJ20050144 (2005).","journal-title":"Biochem. J."},{"key":"75615_CR44","doi-asserted-by":"publisher","first-page":"19574","DOI":"10.1074\/jbc.M400162200","volume":"279","author":"AE Reszko","year":"2004","unstructured":"Reszko, A. E. et al. Peroxisomal fatty acid oxidation is a substantial source of the acetyl moiety of malonyl-CoA in rat heart. J. Biol. Chem. 279, 19574\u201319579. https:\/\/doi.org\/10.1074\/jbc.M400162200 (2004).","journal-title":"J. Biol. Chem."},{"key":"75615_CR45","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1016\/j.ymgme.2010.03.011","volume":"100","author":"AC Maher","year":"2010","unstructured":"Maher, A. C., Mohsen, A. W., Vockley, J. & Tarnopolsky, M. A. Low expression of long-chain acyl-CoA dehydrogenase in human skeletal muscle. Mol. Genet. Metab. 100, 163\u2013167. https:\/\/doi.org\/10.1016\/j.ymgme.2010.03.011 (2010).","journal-title":"Mol. Genet. Metab."},{"key":"75615_CR46","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1016\/j.bbalip.2009.05.006","volume":"1791","author":"M Chegary","year":"2009","unstructured":"Chegary, M. et al. Mitochondrial long chain fatty acid beta-oxidation in man and mouse. Biochim. Biophys. Acta 1791, 806\u2013815. https:\/\/doi.org\/10.1016\/j.bbalip.2009.05.006 (2009).","journal-title":"Biochim. Biophys. Acta"},{"key":"75615_CR47","doi-asserted-by":"publisher","first-page":"101253","DOI":"10.1016\/j.redox.2019.101253","volume":"26","author":"Y Zhang","year":"2019","unstructured":"Zhang, Y., Bharathi, S. S., Beck, M. E. & Goetzman, E. S. The fatty acid oxidation enzyme long-chain acyl-CoA dehydrogenase can be a source of mitochondrial hydrogen peroxide. Redox Biol. 26, 101253. https:\/\/doi.org\/10.1016\/j.redox.2019.101253 (2019).","journal-title":"Redox Biol."},{"key":"75615_CR48","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2020.04.005","author":"ME Beck","year":"2020","unstructured":"Beck, M. E. et al. The common K333Q polymorphism in long-chain acyl-CoA dehydrogenase (LCAD) reduces enzyme stability and function. Mol. Genet. Metab. https:\/\/doi.org\/10.1016\/j.ymgme.2020.04.005 (2020).","journal-title":"Mol. Genet. Metab."},{"key":"75615_CR49","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/j.nbd.2010.09.016","volume":"41","author":"C Glorioso","year":"2011","unstructured":"Glorioso, C., Oh, S., Douillard, G. G. & Sibille, E. Brain molecular aging, promotion of neurological disease and modulation by sirtuin 5 longevity gene polymorphism. Neurobiol. Dis. 41, 279\u2013290. https:\/\/doi.org\/10.1016\/j.nbd.2010.09.016 (2011).","journal-title":"Neurobiol. Dis."},{"key":"75615_CR50","doi-asserted-by":"publisher","first-page":"2384","DOI":"10.1681\/ASN.2019020163","volume":"30","author":"T Chiba","year":"2019","unstructured":"Chiba, T. et al. Sirtuin 5 regulates proximal tubule fatty acid oxidation to protect against AKI. J. Am. Soc. Nephrol. 30, 2384\u20132398. https:\/\/doi.org\/10.1681\/ASN.2019020163 (2019).","journal-title":"J. Am. Soc. Nephrol."},{"key":"75615_CR51","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1007\/978-1-4939-7831-1_8","volume":"1782","author":"T Komlodi","year":"2018","unstructured":"Komlodi, T. et al. Comparison of mitochondrial incubation media for measurement of respiration and hydrogen peroxide production. Methods Mol. Biol. 1782, 137\u2013155. https:\/\/doi.org\/10.1007\/978-1-4939-7831-1_8 (2018).","journal-title":"Methods Mol. Biol."},{"key":"75615_CR52","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1002\/hep.30270","volume":"69","author":"JO Russell","year":"2019","unstructured":"Russell, J. O. et al. Hepatocyte-specific beta-catenin deletion during severe liver injury provokes cholangiocytes to differentiate into hepatocytes. Hepatology 69, 742\u2013759. https:\/\/doi.org\/10.1002\/hep.30270 (2019).","journal-title":"Hepatology"},{"key":"75615_CR53","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.1021\/ac60358a074","volume":"47","author":"JA Thompson","year":"1975","unstructured":"Thompson, J. A. & Markey, S. P. Quantitative metabolic profiling of urinary organic acids by gas chromatography-mass spectrometry: Comparison of isolation methods. Anal. Chem. 47, 1313\u20131321. https:\/\/doi.org\/10.1021\/ac60358a074 (1975).","journal-title":"Anal. Chem."},{"key":"75615_CR54","doi-asserted-by":"publisher","first-page":"1674","DOI":"10.1093\/clinchem\/24.10.1674","volume":"24","author":"SC Gates","year":"1978","unstructured":"Gates, S. C., Dendramis, N. & Sweeley, C. C. Automated metabolic profiling of organic acids in human urine. I. Description of methods. Clin. Chem. 24, 1674\u20131679 (1978).","journal-title":"Clin. Chem."},{"key":"75615_CR55","doi-asserted-by":"publisher","first-page":"33837","DOI":"10.1074\/jbc.M113.510354","volume":"288","author":"SS Bharathi","year":"2013","unstructured":"Bharathi, S. S. et al. Sirtuin 3 (SIRT3) protein regulates long-chain acyl-CoA dehydrogenase by deacetylating conserved lysines near the active site. J. Biol. Chem. 288, 33837\u201333847. https:\/\/doi.org\/10.1074\/jbc.M113.510354 (2013).","journal-title":"J. Biol. Chem."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75615-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75615-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75615-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T22:19:50Z","timestamp":1670365190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-75615-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,27]]},"references-count":55,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["75615"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-75615-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,27]]},"assertion":[{"value":"2 April 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"8 October 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 October 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"18367"}}