Dickkopf-1 promotes the differentiation and adipocytokines secretion via canonical Wnt signaling pathway in primary cultured human preadipocytes

卷:10

Lu, Hongyun ; Li, Xiaofeng ; Mu, Panwei ; Qian, Baiying ; Jiang, Wei ; Zeng, Longyi

Sun Yat Sen Univ

关键词: Human adipose-derived stem cells (ASCs);    Wnt signaling pathway;    Dickkopf 1;    Differentiation;    Adipocytokines secretion;   

DOI  :  10.1016/j.orcp.2015.08.016

学科分类：食品科学和技术

【 摘 要 】

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-gamma and C/EBP-alpha, down-regulating Wnt3a, Wnt10b and beta-catenin, without affecting non-canonical Wnt signaling marker (Wnt5a). In addition, rhDKK-1 treatment increased the secretion of leptin, RBP4, TNF-alpha 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. (C) 2015 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.