{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T21:50:22Z","timestamp":1747173022915,"version":"3.40.5"},"reference-count":45,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T00:00:00Z","timestamp":1681430400000},"content-version":"unspecified","delay-in-days":103,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Nutr Sci"],"published-print":{"date-parts":[[2023]]},"abstract":"<jats:title>Abstract<\/jats:title>\n\t  <jats:p>The iron-regulatory hormone hepcidin is transcriptionally up-regulated by gluconeogenic signals. Recent evidence suggeststhat increases in circulating hepcidin may decrease dietary iron absorption following prolonged exercise, however evidence is limited on whether gluconeogenic signals contribute to post-exercise increases in hepcidin. Mice with genetic knockout of regulated in development and DNA response-1 (REDD1) display greater glycogen depletion following exercise, possibly indicating greater gluconeogenesis. The objective of the present study was to determine liver hepcidin, markers of gluconeogenesis and iron metabolism in REDD1 knockout and wild-type mice following prolonged exercise. Twelve-week-old male REDD1 knockout and wild-type mice were randomised to rest or 60 min treadmill running with 1, 3 or 6 h recovery (<jats:italic>n =<\/jats:italic> 5\u20138\/genotype\/group). Liver gene expression of hepcidin (<jats:italic>Hamp<\/jats:italic>) and gluconeogenic enzymes (<jats:italic>Ppargc1a<\/jats:italic>, <jats:italic>Creb3l3<\/jats:italic>, <jats:italic>Pck1<\/jats:italic>, <jats:italic>Pygl<\/jats:italic>) were determined by qRT-PCR. Effects of genotype, exercise and their interaction were assessed by two-way ANOVAs with Tukey's <jats:italic>post-hoc<\/jats:italic> tests, and Pearson correlations were used to assess the relationships between <jats:italic>Hamp<\/jats:italic> and study outcomes. Liver <jats:italic>Hamp<\/jats:italic> increased 1- and 4-fold at 3 and 6 h post-exercise, compared to rest (<jats:italic>P<\/jats:italic>-adjusted &lt; 0\u22c5009 for all), and was 50% greater in REDD1 knockout compared to wild-type mice (<jats:italic>P<\/jats:italic> = 0\u22c50015). Liver <jats:italic>Ppargc1a<\/jats:italic>, <jats:italic>Creb3l3<\/jats:italic> and <jats:italic>Pck1<\/jats:italic> increased with treadmill running (<jats:italic>P<\/jats:italic> &lt; 0\u22c50001 for all), and liver <jats:italic>Ppargc1a<\/jats:italic>, <jats:italic>Pck1<\/jats:italic> and <jats:italic>Pygl<\/jats:italic> were greater with REDD1 deletion (<jats:italic>P<\/jats:italic> &lt; 0\u22c502 for all). Liver <jats:italic>Hamp<\/jats:italic> was positively correlated with liver <jats:italic>Creb3l3<\/jats:italic> (<jats:italic>R<\/jats:italic> = 0\u22c562, <jats:italic>P<\/jats:italic> &lt; 0\u22c50001) and <jats:italic>Pck1<\/jats:italic> (<jats:italic>R<\/jats:italic> = 0\u22c544, <jats:italic>P<\/jats:italic> = 0\u22c50014). In conclusion, REDD1 deletion and prolonged treadmill running increased liver <jats:italic>Hamp<\/jats:italic> and gluconeogenic regulators of <jats:italic>Hamp<\/jats:italic>, suggesting gluconeogenic signalling of hepcidin with prolonged exercise.<\/jats:p>","DOI":"10.1017\/jns.2023.37","type":"journal-article","created":{"date-parts":[[2023,4,14]],"date-time":"2023-04-14T10:57:46Z","timestamp":1681469866000},"source":"Crossref","is-referenced-by-count":1,"title":["REDD1 deletion and treadmill running increase liver hepcidin and gluconeogenic enzymes in male mice"],"prefix":"10.1017","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9940-0818","authenticated-orcid":false,"suffix":"Jr","given":"David E.","family":"Barney","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bradley 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