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ID 117375
Title Alternative
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
Author
Bavuu, Oyunbileg Tokushima University
Fukuda, Daiju Tokushima University|Osaka Metropolitan University KAKEN Search Researchers
Ganbaatar, Byambasuren Tokushima University
Keywords
Esaxerenone
Mineralocorticoid receptor
Aldosterone
Insulin resistance
Insulin signaling
Content Type
Thesis or Dissertation
Description
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.
Journal Title
European Journal of Pharmacology
ISSN
00142999
18790712
NCID
AA00639687
AA11527211
Publisher
Elsevier
Volume
931
Start Page
175190
Published Date
2022-08-09
Remark
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
DOI (Published Version)
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
ETD
MEXT report number
甲第3756号
Diploma Number
甲医第1581号
Granted Date
2023-09-30
Degree Name
Doctor of Medical Science
Grantor
Tokushima University
departments
Medical Sciences
University Hospital