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Abstract
This Podcast features a conversation with Shelia Collins, senior author of a Research Article that appears in the 25 July 2017 issue of Science Signaling, about how cardiac natriuretic peptides (NPs) exert their beneficial effects on whole-body metabolism. NPs control blood pressure by acting on the kidneys, but they also affect metabolism by stimulating adipose tissue and skeletal muscle to become more metabolically active. Obese individuals have less of these peptides circulating in their blood, suggesting a connection between NP signaling and obesity. NPs stimulate intracellular signaling by binding to and activating the receptors NPRA and NPRB. A third receptor, the NP clearance receptor (NPRC), antagonizes signaling through NPRA and NPRB by binding to and stimulating the internalization and degradation of NPs. To determine whether the beneficial metabolic effects of NPs were due to the action of these peptides in adipose tissue or in skeletal muscle, Wu et al. knocked out NPRC specifically in these tissues in mice. Although mice lacking NPRC in skeletal muscle responded similarly to a high-fat diet as wild-type mice, mice lacking NPRC in adipose tissue were resistant to many of the detrimental metabolic effects of a high-fat diet. These findings suggest that stimulating NP signaling or inhibiting NPRC in adipose tissue may be a potential strategy for treating metabolic disease.