Exogenous ANP Treatment Ameliorates Myocardial Insulin Resistance and Protects against Ischemia-Reperfusion Injury in Diet-Induced Obesity

被引：8

作者：

Oi, Yuhei ^{[1
]}

Nagoshi, Tomohisa ^{[1
]}

Kimura, Haruka ^{[1
]}

Tanaka, Yoshiro ^{[1
]}

Yoshii, Akira ^{[1
]}

Yasutake, Rei ^{[1
]}

Takahashi, Hirotake ^{[1
]}

Kashiwagi, Yusuke ^{[1
]}

Tanaka, Toshikazu D. ^{[1
]}

Tachibana, Toshiaki ^{[2
]}

Yoshimura, Michihiro ^{[1
]}

机构：

[1] Jikei Univ, Sch Med, Dept Internal Med, Div Cardiol, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan

[2] Jikei Univ, Res Ctr Med Sci, Sch Med, Core Res Facil Basic Sci, 3-25-8 Nishi Shimbashi, Tokyo 1058461, Japan

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2022年 / 23卷 / 15期

关键词：

natriuretic peptide; diet-induced obesity; insulin resistance; ischemia-reperfusion injury; intramyocardial lipid droplet; CARDIAC ENERGY-METABOLISM; HIGH-FAT DIET; NATRIURETIC-PEPTIDE; OXIDATIVE STRESS; HEART; AKT; DYSFUNCTION; MOUSE; ACCUMULATION; INFLAMMATION;

D O I：

10.3390/ijms23158373

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Increasing evidence suggests natriuretic peptides (NPs) coordinate interorgan metabolic crosstalk. We recently reported exogenous ANP treatment ameliorated systemic insulin resistance by inducing adipose tissue browning and attenuating hepatic steatosis in diet-induced obesity (DIO). We herein investigated whether ANP treatment also ameliorates myocardial insulin resistance, leading to cardioprotection during ischemia-reperfusion injury (IRI) in DIO. Mice fed a high-fat diet (HFD) or normal-fat diet for 13 weeks were treated with or without ANP infusion subcutaneously for another 3 weeks. Left ventricular BNP expression was substantially reduced in HFD hearts. Intraperitoneal-insulin-administration-induced Akt phosphorylation was impaired in HFD hearts, which was restored by ANP treatment, suggesting that ANP treatment ameliorated myocardial insulin resistance. After ischemia-reperfusion using the Langendorff model, HFD impaired cardiac functional recovery with a corresponding increased infarct size. However, ANP treatment improved functional recovery and reduced injury while restoring impaired IRI-induced Akt phosphorylation in HFD hearts. Myocardial ultrastructural analyses showed increased peri-mitochondrial lipid droplets with concomitantly decreased ATGL and HSL phosphorylation levels in ANP-treated HFD, suggesting that ANP protects mitochondria from lipid overload by trapping lipids. Accordingly, ANP treatment attenuated mitochondria cristae disruption after IRI in HFD hearts. In summary, exogenous ANP treatment ameliorates myocardial insulin resistance and protects against IRI associated with mitochondrial ultrastructure modifications in DIO. Replenishing biologically active NPs substantially affects HFD hearts in which endogenous NP production is impaired.

引用

页数：18