{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T01:22:23Z","timestamp":1775697743964,"version":"3.50.1"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T00:00:00Z","timestamp":1640736000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["23580173"],"award-info":[{"award-number":["23580173"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Dietary sterols are catabolized into various substances in the intestinal tract. Dietary 3-oxo derivatives of cholesterol and plant sterols (e.g., cholest-4-en-3-one and campest-5-en-3-one) have been shown to have anti-obesity effects. In this study, we tested whether feeding cholest-5-en-3-one (5-cholestenone), a cholesterol metabolite, to db\/db mice protects them from obesity-associated metabolic disorders. In db\/db mice, dietary 5-cholestenone significantly alleviated hepatomegaly and elevated serum triglyceride levels; however, the effect was not sufficient to improve hepatic steatosis and obesity. On the other hand, hyperglycemia and severe hyperinsulinemia in control db\/db mice were markedly attenuated in 5-cholestenone-fed db\/db mice. The production of inflammatory cytokines, such as monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-alpha (TNF\u03b1), was decreased, suggesting that the suppressive actions of 5-cholestenone were attributable to the alleviation of chronic inflammation in db\/db mice. Additionally, 5-cholestenone showed an inhibitory effect on TNF\u03b1-induced nuclear factor kappa B (NF\u03baB) activation in the NF\u03baB luciferase gene reporter assay. These results suggest that obesity-induced abnormal glucose metabolism could be alleviated in 5-cholestenone-fed db\/db mice by reducing the production of inflammatory cytokines through suppression of the NF\u03baB signaling pathway.<\/jats:p>","DOI":"10.3390\/metabo12010026","type":"journal-article","created":{"date-parts":[[2021,12,29]],"date-time":"2021-12-29T23:31:35Z","timestamp":1640820695000},"page":"26","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db\/db) Mice"],"prefix":"10.3390","volume":"12","author":[{"given":"Koji","family":"Nagao","sequence":"first","affiliation":[{"name":"Department of Biological Resource Science, Saga University, 1 Honjo-machi, Saga 840-8502, Japan"},{"name":"Course of Biological Science and Technology, The United Graduate School of Agricultural Sciences, Kagoshima University, Kagoshima 890-0065, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5428-844X","authenticated-orcid":false,"given":"Nao","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Biological Resource Science, Saga University, 1 Honjo-machi, Saga 840-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kunio","family":"Suzuki","sequence":"additional","affiliation":[{"name":"RIKEN Nishina Center, Wako 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Takeshi","family":"Shimizu","sequence":"additional","affiliation":[{"name":"RIKEN Center for Sustainable Resource Science, Wako 351-0198, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Teruyoshi","family":"Yanagita","sequence":"additional","affiliation":[{"name":"Department of Biological Resource Science, Saga University, 1 Honjo-machi, Saga 840-8502, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,29]]},"reference":[{"key":"ref_1","unstructured":"International Diabetes Federation (2021). 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