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In this study, we investigated the effect of inhibiting cortisol regeneration via the enzyme 11\u03b2\u2010hydroxysteroid dehydrogenase type 1 (11\u03b2\u2010HSD1) on the pathophysiology of AN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Method<\/jats:title>\n                    <jats:p>Female C57BL\/6J mice underwent a 7\u2010day activity\u2010based anorexia (ABA) paradigm, involving 3\u2009h daily feeding and free access to wheels, until 25% body weight loss or experiment completion. Mice were orally treated once daily with a potent 11\u03b2\u2010HSD1 inhibitor, DSOK\u20100011, or vehicle. Body weight, food intake, and activity transitions were recorded; plasma corticosterone and cholesterol levels were measured using a fluorometric assay; gut microbiota were analyzed using 16S rRNA sequencing; and hippocampal glial cells were analyzed using immunohistochemistry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DSOK\u20100011\u2010treated mice exhibited a modest but significant increase in postprandial wheel\u2010running activity compared to baseline (4\u20135\u2009p.m.,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018; 5\u20136\u2009p.m.,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.043), whereas vehicle\u2010treated mice showed higher preprandial activity (9\u201310\u2009a.m.,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0229). Gut microbiota analysis revealed increased alpha diversity in ABA mice, with a specific enrichment of the\n                      <jats:italic>Lachnospiraceae<\/jats:italic>\n                      family in the DSOK\u20100011 group. However, DSOK\u20100011 did not significantly affect body weight, food intake, corticosterone, and lipid levels, or hippocampal glial cell populations.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Inhibition of 11\u03b2\u2010HSD1 by DSOK\u20100011 was associated with microbiota alterations and subtle shifts in activity timing under energy\u2010deficient conditions. These findings suggest that peripheral glucocorticoid metabolism may influence microbial and behavioral responses in the ABA model, although its metabolic impact appears limited in the acute phase.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/eat.24557","type":"journal-article","created":{"date-parts":[[2025,9,24]],"date-time":"2025-09-24T14:20:40Z","timestamp":1758723640000},"page":"54-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>DSOK<\/scp>\n                    \u20100011 Potentially Regulates Circadian Misalignment and Affects Gut Microbiota Composition in Activity\u2010Based Anorexia Model"],"prefix":"10.1002","volume":"59","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4441-9896","authenticated-orcid":false,"given":"Hiroki","family":"Kawai","sequence":"first","affiliation":[{"name":"Department of Neuropsychiatry Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"},{"name":"Okayama University Medical School  Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nanami","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5498-551X","authenticated-orcid":false,"given":"Shinji","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of Neuropsychiatry Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences  Okayama Japan"},{"name":"Department of Neuropsychiatry Okayama University Hospital  Okayama Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenji","family":"Miyazaki","sequence":"additional","affiliation":[{"name":"Sumitomo Pharma Co. 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