Natriuretic peptides enhance the oxidative capacity of human skeletal muscle
Natriuretic peptides enhance the oxidative capacity of human skeletal muscle
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DOI：
10.1172/jci64526
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发表时间：
2012-12-01
影响因子：
15.9
通讯作者：
Moro, Cedric
中科院分区：
文献类型：
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作者：
Engeli, Stefan;Birkenfeld, Andreas L.;Moro, Cedric
心脏利钠肽（NP）是人体脂肪细胞脂解的主要激活剂，最近被证明可以控制棕色脂肪产热。在这里，我们调查的生理作用NP对人体骨骼肌的氧化代谢。NP受体A型（NPRA）基因表达与人骨骼肌中的PPAR γ共激活因子-1 α（PGC 1A）和几种氧化磷酸化（OXPHOS）基因的mRNA水平呈正相关。此外，NPRA，PGC 1A和OXPHOS基因的表达协同上调，以响应有氧运动训练在人骨骼肌。在人肌管中，NP以循环GMP依赖性方式诱导PGC-1 α和线粒体OXPHOS基因表达。NP处理增加OXPHOS蛋白表达，脂肪氧化，和最大呼吸独立的线粒体增殖和质量的实质性变化。用NP处理肌管概括了运动训练对体内肌肉脂肪氧化能力的影响。总的来说，这些数据表明，人骨骼肌中NP信号传导的激活增强了线粒体氧化代谢和脂肪氧化。我们建议，NP可能有助于运动训练引起的改善骨骼肌脂肪氧化能力在人类。
Cardiac natriuretic peptides (NP) are major activators of human fat cell lipolysis and have recently been shown to control brown fat thermogenesis. Here, we investigated the physiological role of NP on the oxidative metabolism of human skeletal muscle. NP receptor type A (NPRA) gene expression was positively correlated to mRNA levels of PPAR gamma coactivator-1 alpha (PGC1A) and several oxidative phosphorylation (OXPHOS) genes in human skeletal muscle. Further, the expression of NPRA, PGC1A, and OXPHOS genes was coordinately upregulated in response to aerobic exercise training in human skeletal muscle. In human myotubes, NP induced PGC-1 alpha and mitochondrial OXPHOS gene expression in a cyclic GMP-dependent manner. NP treatment increased OXPHOS protein expression, fat oxidation, and maximal respiration independent of substantial changes in mitochondrial proliferation and mass. Treatment of myotubes with NP recapitulated the effect of exercise training on muscle fat oxidative capacity in vivo. Collectively, these data show that activation of NP signaling in human skeletal muscle enhances mitochondrial oxidative metabolism and fat oxidation. We propose that NP could contribute to exercise training-induced improvement in skeletal muscle fat oxidative capacity in humans.