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Secretion of Wnts by adipose cells has an important role in the control of murine adipogenesis. We present the first evidence that a Wnt antagonist, Dickkopf 1 (Dkk1), is secreted by human preadipocytes and promotes adipogenesis. DKK1 mRNA increases six hours after onset of human adipogenesis and this is followed by an increase in Dkk1 protein. With further differentiation, the mRNA and protein levels progressively decline such that they are undetectable in mature adipocytes. The transient induction in DKK1 correlates with downregulation of cytoplasmic and nuclear beta-catenin levels, this being a surrogate marker of canonical Wnt signalling, and Wnt/beta-catenin transcriptional activity. In addition, constitutive expression of Dkk1 in 3T3-L1 preadipocytes promotes their differentiation, further supporting the functional significance of increased Dkk1 levels during human adipogenesis. Concomitant downregulation of the Dkk1 receptors LRP5 and LRP6 is likely to potentiate the ability of Dkk1 to inhibit Wnt signalling and promote differentiation. Notably, Dkk1 is not expressed in primary murine preadipocytes or cell lines. The involvement of Dkk1 in human but not murine adipogenesis indicates that inter-species differences exist in the molecular control of this process. Given the public health importance of disorders of adipose mass, further knowledge of the pathways involved specifically in human adipocyte differentiation might ultimately be of clinical relevance.

Original publication

DOI

10.1242/jcs.02975

Type

Journal article

Journal

J Cell Sci

Publication Date

15/06/2006

Volume

119

Pages

2613 - 2620

Keywords

3T3-L1 Cells, Adipocytes, Adipogenesis, Animals, Cell Differentiation, Cells, Cultured, Gene Expression Regulation, Humans, Intercellular Signaling Peptides and Proteins, LDL-Receptor Related Proteins, Low Density Lipoprotein Receptor-Related Protein-5, Low Density Lipoprotein Receptor-Related Protein-6, Mice, RNA, Messenger, Signal Transduction, Species Specificity, Wnt Proteins