Natriuretic Peptides/cGMP/cGMP-Dependent Protein Kinase Cascades Promote Muscle Mitochondrial

OBJECTIVE—Natriuretic peptides (NPs) have been character-ized as vascular hormones that regulate vascular tone via guany-lyl cyclase (GC), cyclic GMP (cGMP), and cGMP-dependent protein kinase (cGK). Recent clinical studies have shown that plasma NP levels were lower in subjects with the metabolic syndrome. The present study was conducted to elucidate the roles for NP/cGK cascades in energy metabolism. RESEARCH DESIGN AND METHODS—We used three types of genetically engineered mice: brain NP (BNP) transgenic (BNP-Tg), cGK-Tg, and guanylyl cyclase-A (GCA) heterozygous knockout (GCA/) mice and analyzed the metabolic conse-quences of chronic activation of NP/cGK cascades in vivo. We also examined the effect of NPs in cultured myocytes. RESULTS—BNP-Tg mice fed on high-fat diet were protected against diet-induced obesity and insulin resistance, and cGK-T