Natriuretic Peptides: New Players in Energy Homeostasis

Abstract

In this issue of Diabetes , Miyashita et al. (1) provide compelling new evidence that natriuretic peptides (NPs) play a key role in the regulation of body weight and energy metabolism. In a series of complementary experiments, the investigators show that the NP–cyclic guanosine monophosphate (cGMP) signaling system increases the capacity for fat oxidation, activates mitochondrial biogenesis, and prevents the deleterious effects of a high-fat diet (HFD). NPs are not new players in metabolic regulation. Since the discovery of atrial natriuretic peptide (ANP) in 1980 (2), a large body of work has highlighted the multifaceted roles of NPs in the regulation of blood volume and arterial pressure. NPs are members of a family of structurally similar but genetically distinct endogenous peptide hormones. The NP family consists of at least three mammalian peptides: atrial-, brain-, and C-type (ANP, BNP, and CNP, respectively) (3). ANP and BNP preferentially bind to a particulate guanylyl cyclase (GC) receptor called GC-A, whereas CNP is the physiological ligand for GC-B (4). Through their diuretic, vasodilatory, and antimitogenic properties, the NPs play an important role in the regulation of cardiovascular, renal, and endocrine homeostasis (3–5). New findings by Miyashita et al. convincingly demonstrate that the NP-cGMP system also plays a role in the regulation of fatty acid metabolism and body weight regulation (Fig. 1). The researchers generated a series of mouse models to investigate. BNP transgenic mice, which overexpress BNP in the liver at supraphysiological levels (>100-fold compared with resting level), tended to be leaner than wild-type mice. When challenged with HFD, these mice resisted diet-induced obesity and insulin resistance. They had lower total body fat, increased whole-body oxygen consumption and fat …