title: Glucagon Like Peptide-1 Promotes Adipocyte Differentiation via the Wnt4 Mediated Sequestering of Beta-Catenin.
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.
authors: Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China.
authors: Rui
authors: R
authors: Liu
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao TongUniversity, Shanghai 200080, China.
authors: Na
authors: N
authors: Li
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao TongUniversity, Shanghai 200080, China.
authors: Yi
authors: Y
authors: Lin
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao TongUniversity, Shanghai 200080, China.
authors: Mei
authors: M
authors: Wang
authors: Department of Endocrinology, Shanghai First People's Hospital, Shanghai Jiao TongUniversity, Shanghai 200080, China.
authors: Yongde
authors: Y
authors: Peng
authors: Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Departments of Physiology and Medicine, University of Toronto, Toronto, M5B 1W8, Canada.
authors: Keidren
authors: K
authors: Lewi
authors: Department of Endocrinology, Huashan Hospital, Fudan University, Shanghai 200040, China.|Division of Endocrinology and Metabolism, Keenan Research Centre for Biomedical Science of St. Michael's Hospital, Departments of Physiology and Medicine, University of Toronto, Toronto, M5B 1W8, Canada.
authors: Qinghua
authors: Q
authors: Wang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D052216:Glucagon-Like Peptide 1 / Q000494:pharmacology*; D051379:Mice; D021381:Protein Transport / Q000187:drug effects; D060449:Wnt Signaling Pathway / Q000187:drug effects; D060528:Wnt4 Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D060528:Wnt4 Protein; D051176:beta Catenin; D052216:Glucagon-Like Peptide 1