{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T21:30:00Z","timestamp":1780522200123,"version":"3.54.1"},"reference-count":44,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2016,10,26]],"date-time":"2016-10-26T00:00:00Z","timestamp":1477440000000},"content-version":"vor","delay-in-days":25,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH R01DK104748"],"award-info":[{"award-number":["NIH R01DK104748"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["NIH8 P20\u2010GM103528"],"award-info":[{"award-number":["NIH8 P20\u2010GM103528"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2016,10]]},"abstract":"Abstract<\/jats:title>The transcriptional coactivator PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> plays a central role in hepatic gluconeogenesis. We previously reported that alternative splicing of the PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> gene produces an additional transcript encoding the truncated protein NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>. NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> is co\u2010expressed with PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> and highly induced by fasting in the liver. NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> regulates tissue\u2010specific metabolism, but its role in the liver has not been investigated. Thus, the objective of this study was to determine the role of hepatic NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> in the regulation of gluconeogenesis. Adenovirus\u2010mediated expression of NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> in primary hepatocytes strongly stimulated the expression of key gluconeogenic enzyme genes (PEPCK<\/jats:styled-content> and G6Pase), leading to increased glucose production. To further understand NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> function in hepatic gluconeogenesis in\u00a0vivo, we took advantage of a previously reported FL<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>\u2212\/\u2212<\/jats:sup> mouse line that lacks full\u2010length PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> (FL<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>) but retains a slightly shorter and functionally equivalent form of NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> (NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>254<\/jats:sup>). In FL<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice, NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>254<\/jats:sup> was induced by fasting in the liver and recruited to the promoters of PEPCK<\/jats:styled-content> and G6Pase genes. The enrichment of NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>254<\/jats:sup> at the promoters was closely associated with fasting\u2010induced increase in PEPCK<\/jats:styled-content> and G6Pase gene expression and efficient production of glucose from pyruvate during a pyruvate tolerance test in FL<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>\u2212\/\u2212<\/jats:sup> mice. Moreover, FL<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>\u2212\/\u2212<\/jats:sup> primary hepatocytes showed a significant increase in gluconeogenic gene expression and glucose production after treatment with dexamethasone and forskolin, suggesting that NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>254<\/jats:sup> is sufficient to stimulate the gluconeogenic program in the absence of FL<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic>. Collectively, our findings highlight the role of hepatic NT<\/jats:styled-content>\u2010PGC<\/jats:styled-content>\u20101\u03b1<\/jats:italic> in stimulating gluconeogenic gene expression and glucose production.<\/jats:p>","DOI":"10.14814\/phy2.13013","type":"journal-article","created":{"date-parts":[[2016,10,27]],"date-time":"2016-10-27T00:49:27Z","timestamp":1477529367000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Transcriptional coactivator NT<\/scp>\u2010PGC<\/scp>\u20101\u03b1<\/i> promotes gluconeogenic gene expression and enhances hepatic gluconeogenesis"],"prefix":"10.14814","volume":"4","author":[{"given":"Ji Suk","family":"Chang","sequence":"first","affiliation":[{"name":"Laboratory of Gene Regulation and Metabolism Pennington Biomedical Research Center Baton Rouge 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