Liraglutide and insulin have contrary effects on adipogenesis of human adipose-derived stem cells via wnt pathway

Abstract

Background: Glucagon-like peptide-1 (GLP-1) has been reported to have beneficial impacts on improving human’s metabolism and ameliorating insulin resistance. While insulin is another important and conventional drug in diabetes treatment, but it has an adverse effect on weight gain. Purpose: To make sure whether GLP-1 and insulin play different roles in human adiposederived stem cells (hADSCs). Methods: We examined the in vitro roles and molecular mechanisms of liraglutide, a GLP-1 analogue, and human insulin on hADSCs isolated from subcutaneous adipose tissue. Different concentrations (0, 0.1, 1, 10, 100nM) of liraglutide and insulin were added to proliferation and differentiation medium of hADSCs, respectively. Results: Liraglutide inhibits while insulin promotes the proliferation and differentiation at the concentration of 100nM. Moreover, the levels of GSK-3 increase during differentiation and liraglutide could down-regulate it when compared with insulin. We also find that the activation of phosphorylated GSK-3α and GSK-3β is involved in the differentiation roles. And classical and non-classical Wnt pathways all play roles in the differentiation, which are characterized with the up/down-regulation of the expression of adipogenesis genes such as PPAR-γ and CEBP-α. Conclusion: Liraglutide and insulin have contrary effects on the proliferation and adipogenesis via Wnt pathway in primary cultured ADSCs. Those effects could partly explain the different roles of GLP-1 and insulin on weight gain and insulin resistance.