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ID 117375
タイトル別表記
選択的ミネラルコルチコイド受容体遮断薬であるエサキセレノンは、高脂肪食投与マウスにおけるインスリン感受性を改善する
著者
バヴー, オイウンビレグ 徳島大学大学院医学研究科(医学専攻)
福田, 大受 Tokushima University|Osaka Metropolitan University KAKEN研究者をさがす
Ganbaatar, Byambasuren Tokushima University
キーワード
Esaxerenone
Mineralocorticoid receptor
Aldosterone
Insulin resistance
Insulin signaling
資料タイプ
学位論文
抄録
Background: Esaxerenone is a novel, non-steroidal selective mineralocorticoid receptor (MR) 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.
Materials and methods: 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.
Results: 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.
Conclusion: Esaxerenone ameliorated insulin resistance in HFD-fed mice. Reduction of inflammation and improvement in insulin signaling may underlie the beneficial effects of esaxerenone.
掲載誌名
European Journal of Pharmacology
ISSN
00142999
18790712
cat書誌ID
AA00639687
AA11527211
出版者
Elsevier
931
開始ページ
175190
発行日
2022-08-09
備考
内容要旨・審査要旨・論文本文の公開
本論文は,著者Oyunbileg Bavuuの学位論文として提出され,学位審査・授与の対象となっている。
EDB ID
出版社版DOI
出版社版URL
フルテキストファイル
言語
eng
著者版フラグ
博士論文全文を含む
文科省報告番号
甲第3756号
学位記番号
甲医第1581号
学位授与年月日
2023-09-30
学位名
博士(医学)
学位授与機関
徳島大学
部局
医学系
病院