{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:26:42Z","timestamp":1780316802555,"version":"3.54.1"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T00:00:00Z","timestamp":1646092800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,3,1]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>Metformin is a first-line pharmacotherapy in the treatment of type 2 diabetes, a condition closely associated with non-alcoholic fatty liver disease (NAFLD). Although metformin promotes weight loss and improves insulin sensitivity, its effect on intrahepatic triglyceride (IHTG) remains unclear. We investigated the effect of metformin on IHTG, hepatic <jats:italic>de novo<\/jats:italic> lipogenesis (DNL), and fatty acid (FA) oxidation <jats:italic>in vivo<\/jats:italic> in humans.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design and methods<\/jats:title>\n<jats:p>Metabolic investigations, using stable-isotope tracers, were performed in ten insulin-resistant, overweight\/obese human participants with NAFLD who were treatment na\u00efve before and after 12 weeks of metformin treatment. The effect of metformin on markers of s.c. adipose tissue FA metabolism and function, along with the plasma metabolome, was investigated.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Twelve weeks of treatment with metformin resulted in a significant reduction in body weight and improved insulin sensitivity, but IHTG content and FA oxidation remained unchanged. Metformin treatment was associated with a significant decrease in VLDL-triglyceride (TG) concentrations and a significant increase in the relative contribution of DNL-derived FAs to VLDL-TG. There were subtle and relatively few changes in s.c. adipose tissue FA metabolism and the plasma metabolome with metformin treatment.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>We demonstrate the mechanisms of action of metformin whereby it improves insulin sensitivity and promotes weight loss, without improvement in IHTG; these observations are partly explained through increased hepatic DNL and a lack of change in FA oxidation.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-21-0850","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T19:13:01Z","timestamp":1642446781000},"page":"367-377","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":26,"title":["Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis"],"prefix":"10.1093","volume":"186","author":[{"given":"Charlotte J","family":"Green","sequence":"first","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Marjot","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"},{"name":"2Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, University of Oxford, John Radcliffe Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Walsby-Tickle","sequence":"additional","affiliation":[{"name":"3Chemistry Research Laboratory, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catriona","family":"Charlton","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Cornfield","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5315-7963","authenticated-orcid":true,"given":"Felix","family":"Westcott","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine E","family":"Pinnick","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Moolla","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan M","family":"Hazlehurst","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"},{"name":"4Institute of Metabolism and Systems Research, University of Birmingham, Edgbaston, Birmingham, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"McCullagh","sequence":"additional","affiliation":[{"name":"3Chemistry Research Laboratory, University of Oxford, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeremy W","family":"Tomlinson","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"},{"name":"5NIHR Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leanne","family":"Hodson","sequence":"additional","affiliation":[{"name":"1Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Churchill Hospital, Oxford, UK"},{"name":"5NIHR Oxford Biomedical Research Centre, Oxford University Hospital Trusts, Oxford, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/186\/3\/EJE-21-0850.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/186\/3\/EJE-21-0850.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:17:13Z","timestamp":1676391433000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/186\/3\/367\/6850831"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,1]]},"references-count":0,"journal-issue":{"issue":"3"},"URL":"https:\/\/doi.org\/10.1530\/eje-21-0850","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,1]]}}}