title: Dickkopf-1 promotes the differentiation and adipocytokines secretion via canonical Wnt signaling pathway in primary cultured human preadipocytes.
abstract: Dickkopf-1, a newly recognized antagonist for canonical Wnt signaling, is secreted in the early stage of human adipose-derived stem cells (ASCs) adipogenic differentiation. This study was aimed to investigate whether human recombinant DKK-1 (rhDKK-1) could affect the differentiation and metabolism as well as adipocytokines secretion in primary cultured human ASCs.
  
  
  
  Human ASCs were isolated from omental adipose tissue and induced to adipogenic differentiation in the absence or presence of Wnt signaling antagonist rhDKK-1 and agonist SB216763, respectively. mRNA and protein expression profiles of adipogenic factors during the differentiation process were analyzed using quantitative RT-PCR and Western blotting. Adipocytokines secretion levels in the culture medium were measured by ELISA method.
  
  
  
  Our results showed that DKK-1 was already expressed during the early stage of adipogenesis and reached the peak on the 9th day. Exogenous rhDKK-1 exposure accelerated the differentiation by up-regulating PPAR-γ and C/EBP-α, down-regulating Wnt3a, Wnt10b and β-catenin, without affecting non-canonical Wnt signaling marker (Wnt5a). In addition, rhDKK-1 treatment increased the secretion of leptin, RBP4, TNF-α and adiponectin during differentiation. rhDKK-1 treatment also significantly increased the intracellular accumulation of lipids and lipolysis. Thus, Wnt signal pathway agonist SB216763 down-regulated DKK-1 transcriptional and secretion levels during adipogenic process.
  
  
  
  Our results suggest that rhDKK-1 could promote ASCs differentiation and increase adipocytokines secretion via canonical Wnt signaling pathway.
authors.affiliation: Department of Endocrinology & Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou 510630, China; Department of Endocrinology & Metabolism, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong, Zhuhai 519000, China.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Endocrinology & Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou 510630, China.
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Endocrinology & Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou 510630, China.
authors.forename: Panwei
authors.initials: P
authors.lastname: Mu
authors.affiliation: Department of Nephrology, the Fifth Affiliated Hospital of Sun Yat-sen University, Guangdong, Zhuhai 519000, China.
authors.forename: Baiying
authors.initials: B
authors.lastname: Qian
authors.affiliation: Department of Endocrinology & Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou 510630, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Jiang
authors.affiliation: Department of Endocrinology & Metabolism, the Third Affiliated Hospital of Sun Yat-sen University, Guangdong, Guangzhou 510630, China. Electronic address: ly_zeng@yeah.net.
authors.forename: Longyi
authors.initials: L
authors.lastname: Zeng
mesh_terms: D017667:Adipocytes / Q000378:metabolism*; D050156:Adipogenesis; D054392:Adipokines / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D002454:Cell Differentiation; D002478:Cells, Cultured; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D050356:Lipid Metabolism; D009765:Obesity / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D054839:Retinol-Binding Proteins, Plasma / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051153:Wnt Proteins / Q000378:metabolism; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
chemical_list: D054392:Adipokines; D022762:CCAAT-Enhancer-Binding Proteins; C515848:CEBPA protein, human; C501126:DKK1 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; C101326:RBP4 protein, human; D054839:Retinol-Binding Proteins, Plasma; D014409:Tumor Necrosis Factor-alpha; D051153:Wnt Proteins; D051176:beta Catenin
keywords: Adipocytokines secretion; Dickkopf 1; Differentiation; Human adipose-derived stem cells (ASCs); Wnt signaling pathway