Dickkopf-1 promotes the differentiation and adipocytokines secretion via canonical Wnt signaling pathway in primary cultured human preadipocytes.
Obes Res Clin Pract
; 10(4): 454-64, 2016.
Article
em En
| MEDLINE
| ID: mdl-26383960
ABSTRACT
OBJECTIVE:
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.METHODS:
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.RESULTS:
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 ß-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.CONCLUSIONS:
Our results suggest that rhDKK-1 could promote ASCs differentiation and increase adipocytokines secretion via canonical Wnt signaling pathway.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Tecido Adiposo
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Adipócitos
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Peptídeos e Proteínas de Sinalização Intercelular
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Adipogenia
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Adipocinas
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Via de Sinalização Wnt
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Obesidade
Limite:
Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article