{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T04:54:35Z","timestamp":1696481675347},"reference-count":48,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T00:00:00Z","timestamp":1355788800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecular Nutrition Food Res"],"published-print":{"date-parts":[[2013,3]]},"abstract":"<jats:sec><jats:title>Scope<\/jats:title><jats:p>Fasting leads to a significant downregulation of the hypothalamus\u2010pituitary\u2010thyroid axis, and peroxisome proliferator\u2010activated receptor (<jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>) \u03b1 is a key transcription factor in mediating a magnitude of adaptive responses to fasting. In this study, we examined the role of <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 in regulation of the hypothalamus\u2010pituitary\u2010thyroid axis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>Thyroid\u2010stimulating hormone \u03b2\u2010subunit (<jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u03b2) m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> abundance was being reduced in response to treatment of <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>\u03b1<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>1 cells with <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 agonists (<jats:italic>p<\/jats:italic> &lt; 0.05), indicating an inhibitory transcriptional regulation of <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u03b2 by <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1. As expected, fasting significantly downregulated <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u03b2 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression in a two\u2010factorial study with fed or fasted wild\u2010type (<jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>) and <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 knockout mice (<jats:italic>p<\/jats:italic> &lt; 0.05). In contrast to the in vitro data, fasted <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 knockout mice revealed lower m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> concentrations of pituitary <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u03b2 (\u221264%) and <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u2010regulated thyroid genes, and lower plasma concentrations of thyroxine (<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>4, \u221225%), triiodothyronine (<jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>3, \u221225%), free <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>4 (\u221260%), and free <jats:styled-content style=\"fixed-case\">T<\/jats:styled-content>3 (\u221235%) than fasted <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice (<jats:italic>p<\/jats:italic> &lt; 0.05). Those differences were not observed in fed mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Data from thyrotrope cells revealed that <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 could contribute to the fasting\u2010associated downregulation of the <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u03b2 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> expression. In a mouse model, fasting led to a significant reduction in <jats:styled-content style=\"fixed-case\">TSH<\/jats:styled-content>\u03b2 m<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content> level, but unexpectedly this effect was stronger in mice lacking <jats:styled-content style=\"fixed-case\">PPAR<\/jats:styled-content>\u03b1 than in <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content> mice.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mnfr.201200409","type":"journal-article","created":{"date-parts":[[2012,12,18]],"date-time":"2012-12-18T20:03:50Z","timestamp":1355861030000},"page":"376-389","source":"Crossref","is-referenced-by-count":4,"title":["<scp>PPAR<\/scp>\u03b1 modulates the <scp>TSH<\/scp> \u03b2\u2010subunit m<scp>RNA<\/scp> expression in thyrotrope <scp>T<\/scp>\u03b1<scp>T<\/scp>1 cells and in a mouse model"],"prefix":"10.1002","volume":"57","author":[{"given":"Nicole","family":"Wege","sequence":"first","affiliation":[{"name":"Institute of Agricultural and Nutritional Sciences Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Schutkowski","sequence":"additional","affiliation":[{"name":"Institute of Agricultural and Nutritional Sciences Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"K\u00f6nig","sequence":"additional","affiliation":[{"name":"Institute of Agricultural and Nutritional Sciences Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corinna","family":"Brandsch","sequence":"additional","affiliation":[{"name":"Institute of Agricultural and Nutritional Sciences Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Weiwad","sequence":"additional","affiliation":[{"name":"Max Planck Research Unit for Enzymology of Protein Folding  Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele I.","family":"Stangl","sequence":"additional","affiliation":[{"name":"Institute of Agricultural and Nutritional Sciences Martin\u2010Luther\u2010University Halle\u2010Wittenberg  Halle (Saale) Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,12,18]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-003-3216-3"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1089\/thy.2007.0253"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/801609"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000180307"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1677\/joe.0.1740121"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1089\/105072503321319477"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1677\/jme.1.01892"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.139.11.4476"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-5793(00)01364-8"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2005.08.029"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3109\/14756360903468171"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-121-2-770"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.136.8.3480"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10858"},{"key":"e_1_2_7_16_1","doi-asserted-by":"crossref","first-page":"3624","DOI":"10.1210\/endo.138.9.5412","article-title":"Thyrotropin regulation by thyroid hormone in thyroid hormone receptor beta\u2010deficient mice","volume":"138","author":"Weiss R. 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