徳島大学 教育・研究者情報データベース(EDB)

1. (英) Bavuu O / (日) Bavuu Oyunbileg / (読) ばゔ おいうんびれぐ

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2. 福田 大受

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3. (英) Ganbaatar B / (日) GANBAATAR BYAMBASUREN / (読) がんばとる びやんばすれん

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4. 松浦 朋美([徳島大学.病院.先端医科医療開発研究プロジェクト]/[徳島大学.病院.診療科.内科.循環器内科])

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5. 伊勢 孝之([徳島大学.病院.先端医科医療開発研究プロジェクト]/[徳島大学.病院.診療科.内科.循環器内科])

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6. 楠瀬 賢也

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7. 山口 浩司([徳島大学.大学院医歯薬学研究部.医学域.先端医学教育研究プロジェクト]/[徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学]/[徳島大学.病院.診療科.内科.循環器内科])

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8. 八木 秀介([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.地域・家庭医療学])

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9. 山田 博胤([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).地域循環器内科学])

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10. 添木 武([徳島大学.大学院医歯薬学研究部.医学域.連携研究部門(医学域).寄附講座系(医学域).実践地域診療・医科学])

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11. 若槻 哲三

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12. 佐田 政隆([徳島大学.大学院医歯薬学研究部.医学域.医科学部門.内科系.循環器内科学])

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(英) Esaxerenone, a selective mineralocorticoid receptor blocker, improves insulin sensitivity in mice consuming high-fat diet.

(英) Esaxerenone is a novel, non-steroidal selective mineralocorticoid receptor (Csige et al.) blocker. MR activation plays a crucial role in the development of cardiovascular and metabolic diseases. In this study, we investigated the effects of esaxerenone on various metabolic parameters in mice. Esaxerenone (3 mg/kg/day) was orally administered to high-fat diet (HFD)-fed male C57BL/6 mice. Mice fed a normal diet (ND) served as controls. Glucose and insulin tolerance, plasma lipid levels, and transaminase levels were assessed as metabolic parameters. Macrophage accumulation in the adipose tissue was evaluated using histological analysis. 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes were used for in vitro experiments. Gene expression and insulin signaling were examined using quantitative RT-PCR and western blotting, respectively. HFD successfully induced insulin resistance compared with that in ND. Esaxerenone ameliorated insulin resistance (P < 0.05) without altering other metabolic parameters, such as the lipid profile. Esaxerenone administration tended to decrease plasma transaminase levels compared with those in the non-treated group. In the adipose tissue, esaxerenone decreased macrophage accumulation (P < 0.05) and increased the expression levels of adiponectin and PPARγ. Aldosterone significantly decreased the expression levels of PPARγ and adiponectin in 3T3-L1 adipocytes. Furthermore, aldosterone attenuated insulin-induced Akt phosphorylation in 3T3-L1 adipocytes, HepG2 cells, and C2C12 myotubes in a dose-dependent manner (P < 0.01). These effects were ameliorated by pretreatment with esaxerenone. Esaxerenone ameliorated insulin resistance in HFD-fed mice. Reduction of inflammation and improvement in insulin signaling may underlie the beneficial effects of esaxerenone.

1. (英) Article.ELocationID: S0014-2999(22)00451-4

2. (英) Article.ELocationID: 10.1016/j.ejphar.2022.175190

3. (英) Article.PublicationTypeList.PublicationType: Journal Article

4. (英) KeywordList.Keyword: Aldosterone

5. (英) KeywordList.Keyword: Esaxerenone

6. (英) KeywordList.Keyword: Insulin resistance

7. (英) KeywordList.Keyword: Insulin signaling

8. (英) KeywordList.Keyword: Mineralocorticoid receptor

9. (英) CoiStatement: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.