Vasonatrin peptide, a new regulator of adiponectin and interleukin-6 production in adipocytes

Background: In addition to lipolytic function, ANP plays regulatory roles in the production of various adipokines including Adiponectin, Leptin, and interleukins. However, the adipose effects of vasonatrin peptide (VNP), a new manmade natriuretic peptide, are largely unknown.

Aim: The aim of the present study was to identify the roles of VNP on adipokines production, as well as signaling pathways involved. MATERIAL, SUBJECTS, AND METHODS: 3T3-L1 cells were differentiated into adipocytes and exposed to various concentrations of VNP. Quantitative PCR and immunoassays were performed to determine the mRNA and protein levels of Adiponectin and interleukin-6 (IL-6), respectively. The involved signaling pathway was identified by radioimmunoassay to detect the levels of intracellular cyclic GMP (cGMP), mimicking experiments using 8-brcGMP (a membrane-permeable cGMP analog). Also, blocking experiments were performed using HS-142-1, an antagonist of particulate guanylyl cyclase-coupled natriuretic peptide receptor (NPR), or KT-5823, the cGMP-dependent protein kinase (PKG) inhibitor.

Results: VNP markedly enhanced Adiponectin mRNA expression, as well as protein secretion, however, suppressed IL-6 production in mature adipocytes. In addition, VNP significantly increased the intracellular levels of cGMP. The effects of VNP were mimicked by 8-br-cGMP, whereas inhibited by HS-142-1, or KT-5823.

Conclusions: Taken together, VNP regulates Adiponectin and IL-6 production in adipocytes via guanylyl cyclase-coupled NPR/cGMP/PKG pathway.