{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T22:01:44Z","timestamp":1791583304038,"version":"4.3.4"},"reference-count":63,"publisher":"American Society for Clinical Investigation","issue":"1","funder":[{"name":"NIDDK\/NIH","award":["DK053213-13"],"award-info":[{"award-number":["DK053213-13"]}]},{"name":"NIDDK\/NIH","award":["DK067494"],"award-info":[{"award-number":["DK067494"]}]},{"name":"NIDDK\/NIH","award":["DK081761"],"award-info":[{"award-number":["DK081761"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,1,16]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>We hypothesized that obesity-associated hepatosteatosis is a pathophysiological chemical depot for fat-soluble vitamins and altered normal physiology. Using \u03b1-tocopherol (vitamin E) as a model vitamin, pharmacokinetics and kinetics principles were used to determine whether excess liver fat sequestered \u03b1-tocopherol in women with obesity-associated hepatosteatosis versus healthy controls.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Custom-synthesized deuterated \u03b1-tocopherols (d\n                      <jats:sub>3<\/jats:sub>\n                      - and d\n                      <jats:sub>6<\/jats:sub>\n                      -\u03b1-tocopherols) were administered to hospitalized healthy women and women with hepatosteatosis under investigational new drug guidelines. Fluorescently labeled \u03b1-tocopherol was custom-synthesized for cell studies.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In healthy subjects, 85% of intravenous d\n                      <jats:sub>6<\/jats:sub>\n                      -\u03b1-tocopherol disappeared from the circulation within 20 minutes but reappeared within minutes and peaked at 3\u20134 hours; d\n                      <jats:sub>3<\/jats:sub>\n                      - and d\n                      <jats:sub>6<\/jats:sub>\n                      -\u03b1-tocopherols localized to lipoproteins. Lipoprotein redistribution occurred only in vivo within 1 hour, indicating a key role of the liver in uptake and re-release. Compared with healthy subjects who received 2 mg, subjects with hepatosteatosis had similar d\n                      <jats:sub>6<\/jats:sub>\n                      -\u03b1-tocopherol entry rates into liver but reduced initial release rates (\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001). Similarly, pharmacokinetics parameters were reduced in hepatosteatosis subjects, indicating reduced hepatic d\n                      <jats:sub>6<\/jats:sub>\n                      -\u03b1-tocopherol output. Reductions in kinetics and pharmacokinetics parameters in hepatosteatosis subjects who received 2 mg were echoed by similar reductions in healthy subjects when comparing 5- and 2-mg doses. In vitro, fluorescent-labeled \u03b1-tocopherol localized to lipid in fat-loaded hepatocytes, indicating sequestration.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>The unique role of the liver in vitamin E physiology is dysregulated by excess liver fat. Obesity-associated hepatosteatosis may produce unrecognized hepatic vitamin E sequestration, which might subsequently drive liver disease. Our findings raise the possibility that hepatosteatosis may similarly alter hepatic physiology of other fat-soluble vitamins.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov, NCT00862433.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>National Institute of Diabetes and Digestive and Kidney Diseases and NIH grants DK053213-13, DK067494, and DK081761.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci.insight.133309","type":"journal-article","created":{"date-parts":[[2019,12,10]],"date-time":"2019-12-10T12:01:49Z","timestamp":1575979309000},"source":"Crossref","is-referenced-by-count":41,"title":["Vitamin E sequestration by liver fat in 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