内分泌学
内科学
骨骼肌
一磷酸腺苷
β氧化
化学
脑源性神经营养因子
过氧化物酶体增殖物激活受体
AMP活化蛋白激酶
安普克
蛋白激酶A
神经营养因子
生物
腺苷
受体
医学
激酶
生物化学
新陈代谢
作者
Junichi Matsumoto,Shingo Takada,Takaaki Furihata,Hisanori Nambu,Naoya Kakutani,Shohei Maékawa,Wataru Mizushima,Ikuo Nakano,Arata Fukushima,Takashi Yokota,Shinya Tanaka,Haruka Handa,Hisataka Sabe,Shintaro Kinugawa
出处
期刊:Circulation-heart Failure
[Ovid Technologies (Wolters Kluwer)]
日期:2021-01-01
卷期号:14 (1)
被引量:24
标识
DOI:10.1161/circheartfailure.119.005890
摘要
Background: We recently reported that treatment with rhBDNF (recombinant human brain-derived neurotrophic factor) improved the reduced exercise capacity of mice with heart failure (HF) after myocardial infarction (MI). Since BDNF is reported to enhance fatty acid oxidation, we herein conducted an in vivo investigation to determine whether the improvement in exercise capacity is due to the enhancement of the fatty acid oxidation of skeletal muscle via the AMPKα-PGC1α (adenosine monophosphate-activated protein kinase-ɑ–proliferator-activated receptor-r coactivator-1ɑ) axis. Methods: MI and sham operations were conducted in C57BL/6J mice. Two weeks postsurgery, we randomly divided the MI mice into groups treated with rhBDNF or vehicle for 2 weeks. AMPKα-PGC1α signaling and mitochondrial content in the skeletal muscle of the mice were evaluated by Western blotting and transmission electron microscopy. Fatty acid β-oxidation was examined by high-resolution respirometry using permeabilized muscle fiber. BDNF-knockout mice were treated with 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside, an activator of AMPK. Results: The rhBDNF treatment significantly increased the expressions of phosphorylated AMPKα and PGC1α protein and the intermyofibrillar mitochondrial density in the MI mice. The lowered skeletal muscle mitochondrial fatty acid oxidation was significantly improved in the rhBDNF-treated MI mice. The reduced exercise capacity and mitochondrial dysfunction of the BDNF-knockout mice were improved by 5-aminoimidazole-4-carboxamide-1-beta-d-riboruranoside. Conclusions: Beneficial effects of BDNF on the exercise capacity of mice with HF are mediated through an enhancement of fatty acid oxidation via the activation of AMPKα-PGC1α in skeletal muscle. BDNF may become a therapeutic option to improve exercise capacity as an alternative or adjunct to exercise training.
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