{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T04:25:56Z","timestamp":1787286356659,"version":"build-2736575974"},"reference-count":80,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Fatty liver is associated with increased all-cause mortality. Organic cation transporter 1 (OCT1) is a polyspecific hepatic uptake transporter. OCT1 mediates hepatic uptake of vitamin B1 (thiamine); thus, OCT1 deficiency may impair thiamine availability and consequently reduce glucose-derived energy. Consequently, OCT1-knockout mice exhibit significantly reduced liver fat. In 2% of Europeans and White Americans, common genetic variants markedly reduce OCT1 function. In this study, we used these naturally occurring variants to investigate the influences of reduced OCT1 function on liver fat in humans. We analyzed 2512 whole-body MRI datasets from the Study of Health in Pomerania (SHIP) and validated the findings using 31,594 datasets from the UK Biobank. In both cohorts, OCT1 deficiency was associated with lower fat content in the liver (p = 0.027 in SHIP; p = 2.9 \u00d7 10\u22126 in the UK Biobank), but not in other body compartments. OCT1 deficiency remained an independent predictor after adjustment for age, BMI, daily alcohol consumption, and biological sex. To investigate underlying mechanisms, we used Seahorse assays to show that OCT1-overexpressing cells exhibited increased mitochondrial metabolic activity when glucose was the sole energy source. Our findings warrant further investigation of OCT1 as a potential contributor to the pathogenesis of fatty liver.<\/jats:p>","DOI":"10.3390\/ijms27167422","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T13:14:01Z","timestamp":1787145241000},"page":"7422","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically Determined Loss-of-Function of the Organic Cation Transporter OCT1 Is Associated with Lower Liver Fat Content in Humans"],"prefix":"10.3390","volume":"27","author":[{"given":"Anna K.","family":"Scheurer-B\u00f6hme","sequence":"first","affiliation":[{"name":"Department of General Pharmacology, Institute of Pharmacology, Center of Drug Absorption and Transport (C DAT), University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eileen","family":"Moritz","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology, Institute of Pharmacology, Center of Drug Absorption and Transport (C DAT), University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3553-4315","authenticated-orcid":false,"given":"Stefan","family":"Weiss","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site North, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1884-5784","authenticated-orcid":false,"given":"Robin","family":"B\u00fclow","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site North, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"},{"name":"Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0420-7303","authenticated-orcid":false,"given":"Marie-Luise","family":"Kromrey","sequence":"additional","affiliation":[{"name":"Institute of Diagnostic Radiology and Neuroradiology, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-2816-7168","authenticated-orcid":false,"given":"M. Kamal","family":"Nasr","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site North, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5689-3448","authenticated-orcid":false,"given":"Uwe","family":"V\u00f6lker","sequence":"additional","affiliation":[{"name":"Interfaculty Institute of Genetics and Functional Genomics, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"},{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site North, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"V\u00f6lzke","sequence":"additional","affiliation":[{"name":"Institute for Community Medicine, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Engeli","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology, Institute of Pharmacology, Center of Drug Absorption and Transport (C DAT), University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jens-Peter","family":"K\u00fchn","sequence":"additional","affiliation":[{"name":"Institute and Policlinic for Diagnostic and Interventional Radiology, University Hospital, Carl Gustav Carus University, TU Dresden, 01304 Dresden, Saxony, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8309-094X","authenticated-orcid":false,"given":"Alexander","family":"Teumer","sequence":"additional","affiliation":[{"name":"DZHK (German Centre for Cardiovascular Research), Partner Site North, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"},{"name":"Department of Psychiatry and Psychotherapy, University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1670-5534","authenticated-orcid":false,"given":"Mladen V.","family":"Tzvetkov","sequence":"additional","affiliation":[{"name":"Department of General Pharmacology, Institute of Pharmacology, Center of Drug Absorption and Transport (C DAT), University Medicine Greifswald, 17475 Greifswald, Mecklenburg-Western Pomerania, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1016\/j.jhep.2023.04.036","article-title":"Changing Epidemiology, Global Trends and Implications for Outcomes of NAFLD","volume":"79","author":"Wong","year":"2023","journal-title":"J. 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