{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T19:55:53Z","timestamp":1792007753306,"version":"4.4.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2020,5,7]],"date-time":"2020-05-07T00:00:00Z","timestamp":1588809600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Elevated hepatic <jats:italic toggle=\"yes\">de novo<\/jats:italic> lipogenesis (DNL) is a key distinguishing characteristic of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis. In rodent models of NAFLD, treatment with a surrogate of TVB\u20102640, a pharmacological fatty acid synthase inhibitor, has been shown to reduce hepatic fat and other biomarkers of DNL. The purpose of this phase I clinical study was to test the effect of the TVB\u20102640 in obese men with certain metabolic abnormalities that put them at risk for NAFLD.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Twelve subjects (mean\u00a0\u00b1\u00a0SEM, 42\u00a0\u00b1\u00a02 years, body mass index 37.4\u00a0\u00b1\u00a01.2 kg\/m<jats:sup>2<\/jats:sup>, glucose 103\u00a0\u00b1\u00a02\u00a0mg\/dL, triacylglycerols 196\u00a0\u00b1\u00a027\u00a0mg\/dL, and elevated liver enzymes) underwent 10 days of treatment with TVB\u20102640 at doses ranging from 50\u2010150\u00a0mg\/day. Food intake was controlled throughout the study. Hepatic DNL was measured before and after an oral fructose\/glucose bolus using isotopic labeling with 1\u2010<jats:sup>13<\/jats:sup>C<jats:sub>1<\/jats:sub>\u2010acetate intravenous infusion, followed by measurement of labeled very low\u2010density lipoprotein palmitate via gas chromatography mass spectometry. Substrate oxidation was measured by indirect calorimetry. Across the range of doses, fasting DNL was reduced by up to 90% (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.003). Increasing plasma concentrations of TVB\u20102640 were associated with progressive reductions in the percent of fructose\u2010stimulated peak fractional DNL (R<jats:sup>2<\/jats:sup>\u00a0=\u00a0\u22120.749, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.0003) and absolute DNL area under the curve 6\u00a0hours following fructose\/glucose bolus (R<jats:sup>2<\/jats:sup>\u00a0=\u00a0\u22120.554, <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.005). For all subjects combined, alanine aminotransferase was reduced by 15.8\u00a0\u00b1\u00a08.4% (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.05). Substrate oxidation was unchanged, and safety monitoring revealed that the drug was well tolerated, without an increase in plasma triglycerides. Alopecia occurred in 2 subjects (reversed after stopping the drug), but otherwise no changes were observed in fasting glucose, insulin, ketones, and renal function.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>These data support the therapeutic potential of a fatty acid synthase inhibitor, TVB\u20102640 in particular, in patients with NAFLD and nonalcoholic steatohepatitis.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31000","type":"journal-article","created":{"date-parts":[[2019,10,20]],"date-time":"2019-10-20T14:25:07Z","timestamp":1571581507000},"page":"103-118","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":124,"title":["Fatty Acid Synthase Inhibitor TVB\u20102640 Reduces Hepatic de Novo Lipogenesis in Males With Metabolic Abnormalities"],"prefix":"10.1097","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2803-0274","authenticated-orcid":false,"given":"Majid M.","family":"Syed\u2010Abdul","sequence":"first","affiliation":[{"name":"Department of Nutrition and Exercise Physiology,University of Missouri School of Medicine,Columbia,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5681-1097","authenticated-orcid":false,"given":"Elizabeth J.","family":"Parks","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Exercise Physiology,University of Missouri School of Medicine,Columbia,MO"},{"name":"Department of Medicine,Division of Gastroenterology and Hepatology,University of Missouri School of Medicine,Columbia,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayman H.","family":"Gaballah","sequence":"additional","affiliation":[{"name":"Department of Radiology,University of Missouri School of Medicine,Columbia,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberlee","family":"Bingham","sequence":"additional","affiliation":[{"name":"Department of Nutrition and Exercise Physiology,University of Missouri School of Medicine,Columbia,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ghassan M.","family":"Hammoud","sequence":"additional","affiliation":[{"name":"Department of Medicine,Division of Gastroenterology and Hepatology,University of Missouri School of Medicine,Columbia,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George","family":"Kemble","sequence":"additional","affiliation":[{"name":"Sagimet Biosciences (formerly 3\u2010V Biosciences),Menlo Park,CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Buckley","sequence":"additional","affiliation":[{"name":"Sagimet Biosciences (formerly 3\u2010V Biosciences),Menlo 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