The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice
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-c...
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MDPI AG
2021-12-01
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| author | Koji Nagao Nao Inoue Kunio Suzuki Takeshi Shimizu Teruyoshi Yanagita |
| author_facet | Koji Nagao Nao Inoue Kunio Suzuki Takeshi Shimizu Teruyoshi Yanagita |
| author_sort | Koji Nagao |
| collection | DOAJ |
| description | 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 <i>db</i>/<i>db</i> mice protects them from obesity-associated metabolic disorders. In <i>db</i>/<i>db</i> 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 <i>db</i>/<i>db</i> mice were markedly attenuated in 5-cholestenone-fed <i>db</i>/<i>db</i> mice. The production of inflammatory cytokines, such as monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-alpha (TNFα), was decreased, suggesting that the suppressive actions of 5-cholestenone were attributable to the alleviation of chronic inflammation in <i>db</i>/<i>db</i> mice. Additionally, 5-cholestenone showed an inhibitory effect on TNFα-induced nuclear factor kappa B (NFκB) activation in the NFκB luciferase gene reporter assay. These results suggest that obesity-induced abnormal glucose metabolism could be alleviated in 5-cholestenone-fed <i>db</i>/<i>db</i> mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway. |
| first_indexed | 2024-03-10T00:58:06Z |
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| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-03-10T00:58:06Z |
| publishDate | 2021-12-01 |
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| spelling | doaj.art-d2324a1cf6c046aba9258b35a5ec06392023-11-23T14:39:45ZengMDPI AGMetabolites2218-19892021-12-011212610.3390/metabo12010026The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) MiceKoji Nagao0Nao Inoue1Kunio Suzuki2Takeshi Shimizu3Teruyoshi Yanagita4Department of Biological Resource Science, Saga University, 1 Honjo-machi, Saga 840-8502, JapanDepartment of Biological Resource Science, Saga University, 1 Honjo-machi, Saga 840-8502, JapanRIKEN Nishina Center, Wako 351-0198, JapanRIKEN Center for Sustainable Resource Science, Wako 351-0198, JapanDepartment of Biological Resource Science, Saga University, 1 Honjo-machi, Saga 840-8502, JapanDietary 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 <i>db</i>/<i>db</i> mice protects them from obesity-associated metabolic disorders. In <i>db</i>/<i>db</i> 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 <i>db</i>/<i>db</i> mice were markedly attenuated in 5-cholestenone-fed <i>db</i>/<i>db</i> mice. The production of inflammatory cytokines, such as monocyte chemoattractant protein-1, interleukin-6, and tumor necrosis factor-alpha (TNFα), was decreased, suggesting that the suppressive actions of 5-cholestenone were attributable to the alleviation of chronic inflammation in <i>db</i>/<i>db</i> mice. Additionally, 5-cholestenone showed an inhibitory effect on TNFα-induced nuclear factor kappa B (NFκB) activation in the NFκB luciferase gene reporter assay. These results suggest that obesity-induced abnormal glucose metabolism could be alleviated in 5-cholestenone-fed <i>db</i>/<i>db</i> mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway.https://www.mdpi.com/2218-1989/12/1/265-cholestenonehyperglycemiahyperinsulinemiainflammationobese <i>db</i>/<i>db</i> mouse |
| spellingShingle | Koji Nagao Nao Inoue Kunio Suzuki Takeshi Shimizu Teruyoshi Yanagita The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice Metabolites 5-cholestenone hyperglycemia hyperinsulinemia inflammation obese <i>db</i>/<i>db</i> mouse |
| title | The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice |
| title_full | The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice |
| title_fullStr | The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice |
| title_full_unstemmed | The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice |
| title_short | The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (<i>db</i>/<i>db</i>) Mice |
| title_sort | cholesterol metabolite cholest 5 en 3 one alleviates hyperglycemia and hyperinsulinemia in obese i db i i db i mice |
| topic | 5-cholestenone hyperglycemia hyperinsulinemia inflammation obese <i>db</i>/<i>db</i> mouse |
| url | https://www.mdpi.com/2218-1989/12/1/26 |
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