Matsumoto 2021 Circ Heart Fail
Matsumoto J, Takada S, Furihata T, Nambu H, Kakutani N, Maekawa S, Mizushima W, Nakano I, Fukushima A, Yokota T, Tanaka S, Handa H, Sabe H, Kinugawa S (2021) Brain-derived neurotrophic factor improves impaired fatty acid oxidation via the activation of adenosine monophosphate-activated protein kinase-Ι - proliferator-activated receptor-r coactivator-1Ι signaling in skeletal muscle of mice with heart failure. Circ Heart Fail 14: e005890. |
Matsumoto Jun, Takada Shingo, Furihata Takaaki, Nambu Hideo, Kakutani Naoya, Maekawa Satoshi, Mizushima Wataru, Nakano Ippei, Fukushima Arata, Yokota Takashi, Tanaka Shinya, Handa Haruka, Sabe Hisakata, Kinugawa Shintaro (2021) Circ Heart Fail
Abstract: 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 AMPKΞ±-PGC1Ξ± (adenosine monophosphate-activated protein kinase-Ι-proliferator-activated receptor-r coactivator-1Ι) 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. AMPKΞ±-PGC1Ξ± signaling and mitochondrial content in the skeletal muscle of the mice were evaluated by Western blotting and transmission electron microscopy. Fatty acid Ξ²-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 AMPKΞ± and PGC1Ξ± 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 AMPKΞ±-PGC1Ξ± in skeletal muscle. BDNF may become a therapeutic option to improve exercise capacity as an alternative or adjunct to exercise training. β’ Keywords: brain-derived neurotrophic factor; heart failure; mitochondria; myocardial infarction; skeletal muscle
β’ O2k-Network Lab: JP Sapporo Yokota T
Labels: MiParea: Respiration
Pathology: Cardiovascular
Organism: Mouse Tissue;cell: Skeletal muscle Preparation: Permeabilized tissue
Coupling state: LEAK, OXPHOS
HRR: Oxygraph-2k
2021-01, JP