C-type Natriuretic Peptide Promotes Adipogenic Differentiation of Goat Adipose Derived Stem Cells via cGMP/PKG/ p38 MAPK Signal Pathway

Abstract

BackgroundTwo types of adipose tissue, white adipose and brown adipose, have been identified in mammals. For goat, adipose tissue also plays an important role in improving meat and milk quality. C-type natriuretic peptide (CNP) is a member of natriuretic peptide family. Once CNP binds to natriuretic peptide receptor B (NPR-B), NPR-B induces the production of cGMP, thereby activating PKG and downstream targets. The expression of CNP and NPR-B in adipose tissue led to a hypothesis that CNP could have roles involving in regulation of adipogenesis in goat. However, there are few studies on the relationship between CNP and adipogenesis in goat. In the present study, goat adipose derived stem cells (ADSCs) were isolated and employed to investigate the effect of CNP on adipogenesis in goat.ResultsDuring adipogenic differentiation in goat ADSCs, the expression of NPR-B increased at 4 d and 8 d and reduced at 12 d after differentiation. When goat ADSCs were treated with 100 nM and 1000 nM CNP during adipogenic differentiation, there are more accumulation of lipid droplets in the cytoplasm and the up-regulation in the expression of adipogenesis relative genes including PPAR-γ, FASN and LPL. Interestingly, the expression level of brown adipose genes UCP-1 and PGC-1α were also up-regulated. Furthermore, the cGMP level was increased after treatment with CNP. Adding cGMP analogues 8-pCPT-cGMP (PKG activator) could increase adipogenesis efficiency, and adding both PKG inhibitor Rp-8-CPT-cGMP and CNP inhibited adipogenic differentiation. After treatment with CNP or PKG activator, the phosphorylation of p38 MAPK, MK2 and ATF2 were up-regulated, and their phosphorylation were significantly inhibited when CNP and PKG inhibitor were added simultaneously. SB203580 is the specific inhibitor for p38 MAPK. After treatment with CNP and SB203580 simultaneously, the adipogenic differentiation efficiency of goat ADSCs was significantly inhibited, and the expression of UCP-1 and PGC-1α were also reduced. ConclusionsCNP could promote adipogenic differentiation of goat ADSCs. The stimulative effect of CNP on adipose differentiation depends on the cGMP/PKG/ p38 MAPK signal pathway. Our study will be helpful to understand the regulation mechanism of goat adipose differentiation, especially brown adipose differentiation.