{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T04:32:35Z","timestamp":1789878755274,"version":"4.0.1"},"reference-count":61,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T00:00:00Z","timestamp":1698105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Bergen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Altered hepatic mitochondrial fatty acid \u03b2-oxidation and associated tricarboxylic acid (TCA) cycle activity contributes to lifestyle-related diseases, and circulating biomarkers reflecting these changes could have disease prognostic value. This study aimed to determine hepatic and systemic changes in TCA-cycle-related metabolites upon the selective pharmacologic enhancement of mitochondrial fatty acid \u03b2-oxidation in the liver, and to elucidate the mechanisms and potential markers of hepatic mitochondrial activity. Male Wistar rats were treated with 3-thia fatty acids (e.g., tetradecylthioacetic acid (TTA)), which target mitochondrial biogenesis, mitochondrial fatty acid \u03b2-oxidation, and ketogenesis predominantly in the liver. Hepatic and plasma concentrations of TCA cycle intermediates and anaplerotic substrates (LC-MS\/MS), plasma ketones (colorimetric assay), and acylcarnitines (HPLC-MS\/MS), along with associated TCA-cycle-related gene expression (qPCR) and enzyme activities, were determined. TTA-induced hepatic fatty acid \u03b2-oxidation resulted in an increased ratio of plasma ketone bodies\/nonesterified fatty acid (NEFA), lower plasma malonyl-CoA levels, and a higher ratio of plasma acetylcarnitine\/palmitoylcarnitine (C2\/C16). These changes were associated with decreased hepatic and increased plasma pyruvate concentrations, and increased plasma concentrations of succinate, malate, and 2-hydroxyglutarate. Expression of several genes encoding TCA cycle enzymes and the malate\u2013oxoglutarate carrier (Slc25a11), glutamate dehydrogenase (Gdh), and malic enzyme (Mdh1 and Mdh2) were significantly increased. In conclusion, the induction of hepatic mitochondrial fatty acid \u03b2-oxidation by 3-thia fatty acids lowered hepatic pyruvate while increasing plasma pyruvate, as well as succinate, malate, and 2-hydroxyglutarate.<\/jats:p>","DOI":"10.3390\/ijms242115536","type":"journal-article","created":{"date-parts":[[2023,10,24]],"date-time":"2023-10-24T11:34:47Z","timestamp":1698147287000},"page":"15536","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Changes in Plasma Pyruvate and TCA Cycle Metabolites upon Increased Hepatic Fatty Acid Oxidation and Ketogenesis in Male Wistar Rats"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6972-1824","authenticated-orcid":false,"given":"Simon Nitter","family":"Dankel","sequence":"first","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tine-Lise","family":"Kalleklev","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8829-3412","authenticated-orcid":false,"given":"Siri Lunde","family":"Tungland","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, N-4021 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marit Hallvardsdotter","family":"Stafsnes","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, NTNU Norwegian University of Science and Technology, N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7851-8083","authenticated-orcid":false,"given":"Per","family":"Bruheim","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, NTNU Norwegian University of Science and Technology, N-7491 Trondheim, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Aquinas","family":"Aloysius","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carine","family":"Lindquist","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jon","family":"Skorve","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ottar Kjell","family":"Nyg\u00e5rd","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"},{"name":"Department of Heart Disease, Haukeland University Hospital, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lise","family":"Madsen","sequence":"additional","affiliation":[{"name":"Department of Clinical Medicine, University of Bergen, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9718-5117","authenticated-orcid":false,"given":"Bodil","family":"Bj\u00f8rndal","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"},{"name":"Department of Sports, Food and Natural Sciences, Western Norway University of Applied Sciences, N-5020 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9413-6969","authenticated-orcid":false,"given":"Magne Olav","family":"Sydnes","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Bioscience and Environmental Engineering, University of Stavanger, N-4021 Stavanger, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf Kristian","family":"Berge","sequence":"additional","affiliation":[{"name":"Department of Clinical Science, University of Bergen, N-5021 Bergen, Norway"},{"name":"Department of Heart Disease, Haukeland University Hospital, N-5021 Bergen, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Prasun, P. 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