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We found that CR changed the liver acylcarnitine profile: acetylcarnitine, short\u2010chain acylcarnitines, and long\u2010chain 3\u2010hydroxy\u2010acylcarnitines increased, and several long\u2010chain acylcarnitines decreased. Acetyl\u2010CoA and short\u2010chain acyl\u2010CoAs were also increased in CR. CR did not affect the expression of CPT1 and upregulated the expression of long\u2010chain and very\u2010long\u2010chain Acyl\u2010CoA dehydrogenases (LCAD and VLCAD, respectively). The expression of downstream enzymes such as mitochondrial trifunctional protein and enzymes in medium\u2010 and short\u2010chain acyl\u2010CoAs oxidation was not affected in CR. CR shifted the balance of fatty acid oxidation enzymes and fatty acid metabolites in the liver. Acetyl\u2010CoA generated through beta\u2010oxidation can be used for ketogenesis or energy production. In agreement, blood ketone bodies increased under CR in a time of the day\u2010dependent manner. Carnitine acetyltransferase (CrAT) is a bidirectional enzyme that interconverts short\u2010chain acyl\u2010CoAs and their corresponding acylcarnitines. CrAT expression was induced in CR liver supporting the increased acetylcarnitine and short\u2010chain acylcarnitine production. Acetylcarnitine can freely travel between cellular sub\u2010compartments. Supporting this CR increased protein acetylation in the mitochondria, cytoplasm, and nucleus. We hypothesize that changes in acyl\u2010CoA and acylcarnitine levels help to control energy metabolism and contribute to metabolic flexibility under CR.<\/jats:p>","DOI":"10.1111\/acel.13266","type":"journal-article","created":{"date-parts":[[2020,10,26]],"date-time":"2020-10-26T18:52:51Z","timestamp":1603738371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["CR reprograms acetyl\u2010CoA metabolism and induces long\u2010chain acyl\u2010CoA dehydrogenase and CrAT expression"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9634-0410","authenticated-orcid":false,"given":"Volha","family":"Mezhnina","sequence":"first","affiliation":[{"name":"Center for Gene Regulation in Health and Disease and Department of Biological Geological and Environmental Sciences Cleveland State University  Cleveland Ohio 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