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The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) 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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Autores principales: Nagao, Koji, Inoue, Nao, Suzuki, Kunio, Shimizu, Takeshi, Yanagita, Teruyoshi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779233/
https://www.ncbi.nlm.nih.gov/pubmed/35050148
http://dx.doi.org/10.3390/metabo12010026
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author Nagao, Koji
Inoue, Nao
Suzuki, Kunio
Shimizu, Takeshi
Yanagita, Teruyoshi
author_facet Nagao, Koji
Inoue, Nao
Suzuki, Kunio
Shimizu, Takeshi
Yanagita, Teruyoshi
author_sort Nagao, Koji
collection PubMed
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 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 (TNFα), 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 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 db/db mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway.
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spelling pubmed-87792332022-01-22 The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice Nagao, Koji Inoue, Nao Suzuki, Kunio Shimizu, Takeshi Yanagita, Teruyoshi Metabolites Article 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 (TNFα), 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 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 db/db mice by reducing the production of inflammatory cytokines through suppression of the NFκB signaling pathway. MDPI 2021-12-29 /pmc/articles/PMC8779233/ /pubmed/35050148 http://dx.doi.org/10.3390/metabo12010026 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Nagao, Koji
Inoue, Nao
Suzuki, Kunio
Shimizu, Takeshi
Yanagita, Teruyoshi
The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
title The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
title_full The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
title_fullStr The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
title_full_unstemmed The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
title_short The Cholesterol Metabolite Cholest-5-en-3-One Alleviates Hyperglycemia and Hyperinsulinemia in Obese (db/db) Mice
title_sort cholesterol metabolite cholest-5-en-3-one alleviates hyperglycemia and hyperinsulinemia in obese (db/db) mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779233/
https://www.ncbi.nlm.nih.gov/pubmed/35050148
http://dx.doi.org/10.3390/metabo12010026
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