FIG. 1.

Proposed role of ANP and BNP in energy metabolism under conditions of normal diet and activity levels vs. HFD and inactivity. ANP and BNP induce cGMP signaling through GC-A, whereas NPR-C inactivates these same peptides. The functional balance of GC-A to NPR-C therefore regulates their biological effect at the tissue level. cGMP/cGK signaling promotes lipolysis and adiponectin secretion in adipose tissue and mitochondrial biogenesis and fat oxidation in skeletal muscle (left panel). This dual action of NPs may confer resistance to obesity and type 2 diabetes. In contrast, reduced GC-A expression and increased NPR-C expression during high-fat feeding and/or inactivity depress cGMP signaling in adipose tissue and muscle leading to increased fat mass, ectopic fat deposition, insulin resistance, and increased susceptibility to type 2 diabetes (right panel).