Natriuretic peptide signaling is involved in the expression of oxidative metabolism-related and muscle fiber constitutive genes in the gastrocnemius muscle.

Natriuretic peptides regulate cyclic guanosine monophosphate (cGMP) levels via their receptors and have various physiological effects. Natriuretic peptide receptor C (NPR-C) increases cGMP signaling by functioning as a clearance receptor. We analyzed the role of natriuretic peptides in the skeletal muscle, which increases in mass with bone elongation, of NPR-C- mice. High-fat diet (HFD)-fed NPR-C- mice exhibited obesity resistance and higher oxygen consumption. PGC1α gene expression was upregulated in the gastrocnemius muscle of HFD-fed NPR-C- mice compared with HFD-fed NPR-C+ (wild-type) mice. Gene expression of proliferator-activated receptor delta and estrogen-related receptor α, which upregulate oxidative metabolism, was increased in the gastrocnemius muscle of NPR-C- mice, irrespective of diet. Expression of myosin heavy chain 7, a component of type I slow-twitch fiber, was enhanced. Natriuretic peptide signaling may influence oxidative metabolism-related and slow-twitch fiber constitutive gene expression in the fast-twitch gastrocnemius muscle but not in slow-twitch muscles such as the soleus.