心筋Sirt1の脂肪毒性抑制作用の解明と拡張障害型心不全への新規治療応用について

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Author: 山本, 恒久

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Publication date: 2017

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Note (General)：: type:textマウスへ飽和脂肪酸リッチな食事を与えたところ, 心筋特異的Sirt1欠損マウス(Sirt1CKO)では拡張障害が強く観察された。SCD1の発現はSirt1CKOでは低く, 膜リン脂質の飽和脂肪酸化(SFA/MUFA比が高い)が観察され, 小胞体ストレスも強く誘導されていた。NMN投...

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科研費研究者番号 : 60626688

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Material Type: 文書・図像類
Title: 心筋Sirt1の脂肪毒性抑制作用の解明と拡張障害型心不全への新規治療応用について
Author/Editor: 山本, 恒久
Author Heading: 山本, 恒久
Publication Date: 2017
Publication Date (W3CDTF): 2017
Alternative Title: シンキン Sirt1 ノシボウドクセイヨクセイサヨウノカイメイトカクチョウショウガイガタシンフゼンエノシンキチリョウオウヨウニツイテ
Shinkin Sirt1 no shibō dokusei yokusei sayō no kaimei to kakuchō shōgaigata shinfuzen eno shinki chiryō ōyō ni tsuite
Investigation for the protective role of cardiac Sirt1 against lipotoxicity and treatment strategy for diastolic dysfunction
Periodical title: 科学研究費補助金研究成果報告書
Text Language Code: jpn
eng
Subject Heading: 肥満,拡張障害,脂肪毒性,Sirt1,NMN,膜の飽和化,脂肪酸組成
Target Audience: 一般
Note (General): type:text
マウスへ飽和脂肪酸リッチな食事を与えたところ, 心筋特異的Sirt1欠損マウス(Sirt1CKO)では拡張障害が強く観察された。SCD1の発現はSirt1CKOでは低く, 膜リン脂質の飽和脂肪酸化(SFA/MUFA比が高い)が観察され, 小胞体ストレスも強く誘導されていた。NMN投与は心筋Sirt1活性を高め, SCD1発現を上昇させた。さらに飽和脂肪酸によるSFA/MUFA比の上昇を低く抑え小胞体ストレスを軽減し, 拡張障害も改善させた。NMNの効果はSirt1CKOでは観察されなかった。 Control and Sirt1 knockout mice (Sirt1CKO) were kept on Saturated fatty acid (SFA)-rich diet from 4 weeks to 20 weeks of age. Nicotinamide mononucleotide (NMN), or PBS was administered intraperitoneally daily for the last week. Pathological cardiac remodeling was exaggerated in Sirt1CKO compared to control. Diastolic function was impaired more severely in Sirt1CKO compared to control. The expression of stearoyl-CoA desaturase-1 (SCD1), which converts SFA to monounsaturated fatty acid (MUFA), was reduced in Sirt1CKO compared to control. In comparison to control, Sirt1CKO had a higher SFA/MUFA ratio in membrane phospholipid and higher ER stress-like response. NMN administration increased cardiac Sirt1 activity, increased the expression of SCD1, decreased the SFA/MUFA ratio in membrane phospholipid, reduced ER stress-like response, and improved diastolic function in control. No such therapeutic effect was observed in Sirt1CKO.
研究種目 : 若手研究(B) 研究期間 : 2016～2017 課題番号 : 16K21358 研究分野 : 循環器内科学
Access Restrictions: 限定公開
Related Material: 科研費研究者番号 : 60626688
Data Provider (Database): 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）
https://irdb.nii.ac.jp
Original Data Provider (Database): 慶應義塾大学 : 慶應義塾大学学術情報リポジトリ