The University of Southampton
University of Southampton Institutional Repository

The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis

The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis
The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis

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 β-catenin levels, this being a surrogate marker of canonical Wnt signalling, and Wnt/β-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.

Adipocyte, Adipogenesis, Dickkopf 1, Human, LRP5, Wnt
0021-9533
2613-2620
Christodoulides, Constantinos
f5ad503b-bd23-4f57-8e5f-4a7d9ab6c7e5
Laudes, Matthias
9789033b-d450-42fd-88d9-39201205595d
Cawthorn, Will P.
3eadef28-0866-4a73-81e7-f08db6f7d731
Schinner, Sven
43378156-7a07-41ec-8b88-96c501a589d2
Soos, Maria
21963a9a-0b14-4122-a9b4-fa294822a52a
O'Rahilly, Stephen
e5c7869f-10d1-4fdc-a564-e4907be415a3
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Vidal-Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036
Christodoulides, Constantinos
f5ad503b-bd23-4f57-8e5f-4a7d9ab6c7e5
Laudes, Matthias
9789033b-d450-42fd-88d9-39201205595d
Cawthorn, Will P.
3eadef28-0866-4a73-81e7-f08db6f7d731
Schinner, Sven
43378156-7a07-41ec-8b88-96c501a589d2
Soos, Maria
21963a9a-0b14-4122-a9b4-fa294822a52a
O'Rahilly, Stephen
e5c7869f-10d1-4fdc-a564-e4907be415a3
Sethi, Jaswinder K.
923f1a81-91e4-46cd-8853-bb4a979f5a85
Vidal-Puig, Antonio
7d46d380-1b9d-40cb-90a3-72679e143036

Christodoulides, Constantinos, Laudes, Matthias, Cawthorn, Will P., Schinner, Sven, Soos, Maria, O'Rahilly, Stephen, Sethi, Jaswinder K. and Vidal-Puig, Antonio (2006) The Wnt antagonist Dickkopf-1 and its receptors are coordinately regulated during early human adipogenesis. Journal of Cell Science, 119 (12), 2613-2620. (doi:10.1242/jcs.02975).

Record type: Article

Abstract

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 β-catenin levels, this being a surrogate marker of canonical Wnt signalling, and Wnt/β-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.

Full text not available from this repository.

More information

Published date: 15 June 2006
Keywords: Adipocyte, Adipogenesis, Dickkopf 1, Human, LRP5, Wnt

Identifiers

Local EPrints ID: 415423
URI: https://eprints.soton.ac.uk/id/eprint/415423
ISSN: 0021-9533
PURE UUID: 5c2523f5-911e-431a-a4c3-1a8eba4747b8
ORCID for Jaswinder K. Sethi: ORCID iD orcid.org/0000-0003-4157-0475

Catalogue record

Date deposited: 09 Nov 2017 17:30
Last modified: 14 Mar 2019 01:25

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×