Journal of Endocrinological Investigation 2011-11-01

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

B-Y Chen, R Tie, P Qu, M-Z Zhu, X-X Zhu, J Jin, J Yu

Index: J. Endocrinol. Invest. 34(10) , 742-6, (2011)

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Abstract

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