Abstract
Glucagon-like peptide-1 (GLP-1) plays a role in the regulation of adipogenesis; however, the precise underlying molecular mechanism has not been fully defined. Wnt was recently identified as an important regulator of adipogenesis. This study aimed to investigate the involvement of the Wnt signaling pathway in the effects of GLP-1 on adipocyte differentiation. 3T3-L1 cells were induced to differentiate. The changes in the expression levels of adipogenic transcription factors and Wnts and the phosphorylation level and subcellular localization of β-catenin were quantified after GLP-1 treatment. GLP-1 stimulated adipocyte differentiation and lipid accumulation, which were accompanied by the expression of adipocyte marker genes. The expression of Wnt4 was upregulated in the process of adipocyte differentiation, which was further enhanced by treatment with GLP-1. β-catenin, an important mediator of the Wnt pathway, was immediately dephosphorylated and translocated from cytoplasm to nucleus when differentiation was induced. In the presence of GLP-1, however, β-catenin was redirected to the cell plasma membrane leading to its decreased accumulation in the nucleus. Knockdown of Wnt4 blocked the effect of GLP-1 on the cellular localization of β-catenin and expression level of adipogenic transcription factors. Our findings showed that GLP-1 promoted adipogenesis through the modulation of the Wnt4/β-catenin signaling pathway, suggesting that the GLP-1-Wntβ-catenin system might be a new target for the treatment of metabolic disease.
Highlights
Chronic nutrient overload causes an increase in adipose depots
We show here that the engagement of Glucagon-like peptide-1 (GLP-1) receptor (GLP-1R) directly regulated the Wnt member 4 (Wnt4)-β-catenin pathway during adipocyte differentiation, providing a mechanism for adipose tissue to adapt to metabolic stress
The effects of GLP-1 on Wnt10 were found to be dose-related; 50 nM of GLP-1 significantly increased the production of Wnt10, while 10 nM had no significant effect (Fig 1A).These data suggested that GLP-1 would regulate adipocyte differentiation through modulation of the wingless-type MMTV integration site family members (Wnts) signaling pathway
Summary
Chronic nutrient overload causes an increase in adipose depots. This effect has often been associated with the development of type 2 diabetes, atherosclerosis, and hyperlipidemia [1;2]. The growth of adipose tissue involves cellular hypertrophy (cell size increase) and hyperplasia (cell number increase) [3]. In adult humans,the recruitment and proliferation of pre-adipocytes occur in addition to adipocyte hypertrophy [4;5]. August 9, 2016 catenin at residues Ser and Thr; GSK3β, glycogen synthase kinase-3β PLOS ONE | DOI:10.1371/journal.pone.0160212 August 9, 2016 catenin at residues Ser and Thr; GSK3β, glycogen synthase kinase-3β
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