Liraglutide and Insulin Have Contrary Effects on Adipogenesis of Human Adipose-Derived Stem Cells via Wnt Pathway

Abstract

Hong Liu,1,2 Yan-li Zhan,2,3 Guo-jing Luo,2,4 Ling-ling Zou,2,5 Yun Li,2 Hong-yun Lu2,4 1Department of Nutrition, The Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 2Department of Endocrinology & Metabolism, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai, Guangdong, People’s Republic of China; 3Department of Rheumatology, Jiaozuo People’s Hospital, Jiaozuo, Henan, People’s Republic of China; 4Department of Endocrinology & Metabolism, Zhuhai Hospital Affiliated with Jinan University, Zhuhai People’s Hospital, Zhuhai, Guangdong, People’s Republic of China; 5Department of Endocrinology, The Second People’s Hospital of Hefei, Anhui, People’s Republic of ChinaCorrespondence: Hong-yun LuDepartment of Endocrinology & Metabolism, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52 Meihua East Road, Zhuhai, Guangdong 519000, People’s Republic of ChinaTel [phone]Fax [phone]Email [email protected]: 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 adipose-derived 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.Keywords: liraglutide, insulin, human adipose-derived stem cells, obesity, Wnt signaling pathway

Keywords

• liraglutide
• insulin
• human adipose derived stem cells
• obesity
• wnt signaling pathway