WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity

Abstract WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the CCN family able to mediate cell growth, transformation and survival in a tissue-specific manner. Here, we report that WISP1 expression was highly increased in preadipocytes and decreased during adipocy...

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Autores principales:	Nathalie Ferrand, Véronique Béreziat, Marthe Moldes, Maurice Zaoui, Annette K. Larsen, Michèle Sabbah
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5b0ca59d5a4540bd99b82b8a5908c4f0
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spelling	oai:doaj.org-article:5b0ca59d5a4540bd99b82b8a5908c4f02021-12-02T16:06:55ZWISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity10.1038/s41598-017-01866-22045-2322https://doaj.org/article/5b0ca59d5a4540bd99b82b8a5908c4f02017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01866-2https://doaj.org/toc/2045-2322Abstract WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the CCN family able to mediate cell growth, transformation and survival in a tissue-specific manner. Here, we report that WISP1 expression was highly increased in preadipocytes and decreased during adipocyte differentiation. Moreover, we observed an increase in WISP1 gene expression in adipose tissue from both diet-induced and leptin-deficient ob/ob obese mice, suggesting that WISP1 could be involved in the pathophysiological onset of obesity. Interestingly, overexpression of WISP1 in 3T3-F442A cells prevented adipocyte differentiation via downregulation of peroxisome proliferator-activated receptor (PPARγ) transcriptional activity thereby attenuating the expression of adipogenic markers. Conversely, silencing of WISP1 enhanced adipocyte differentiation. We further show that the inactivation of PPARγ transcriptional activity was mediated, at least in part, by a direct physical association between WISP1 and PPARγ, followed by proteasome-dependent degradation of PPARγ. These results suggest for the first time that WISP1 interacts with PPARγ and that this interaction results in the inhibition of PPARγ activity. Taken together our results suggest that WISP1 functions as a negative regulator of adipogenesis.Nathalie FerrandVéronique BéreziatMarthe MoldesMaurice ZaouiAnnette K. LarsenMichèle SabbahNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nathalie Ferrand Véronique Béreziat Marthe Moldes Maurice Zaoui Annette K. Larsen Michèle Sabbah WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity
description	Abstract WISP1 (Wnt1-inducible signaling pathway protein-1, also known as CCN4) is a member of the CCN family able to mediate cell growth, transformation and survival in a tissue-specific manner. Here, we report that WISP1 expression was highly increased in preadipocytes and decreased during adipocyte differentiation. Moreover, we observed an increase in WISP1 gene expression in adipose tissue from both diet-induced and leptin-deficient ob/ob obese mice, suggesting that WISP1 could be involved in the pathophysiological onset of obesity. Interestingly, overexpression of WISP1 in 3T3-F442A cells prevented adipocyte differentiation via downregulation of peroxisome proliferator-activated receptor (PPARγ) transcriptional activity thereby attenuating the expression of adipogenic markers. Conversely, silencing of WISP1 enhanced adipocyte differentiation. We further show that the inactivation of PPARγ transcriptional activity was mediated, at least in part, by a direct physical association between WISP1 and PPARγ, followed by proteasome-dependent degradation of PPARγ. These results suggest for the first time that WISP1 interacts with PPARγ and that this interaction results in the inhibition of PPARγ activity. Taken together our results suggest that WISP1 functions as a negative regulator of adipogenesis.
format	article
author	Nathalie Ferrand Véronique Béreziat Marthe Moldes Maurice Zaoui Annette K. Larsen Michèle Sabbah
author_facet	Nathalie Ferrand Véronique Béreziat Marthe Moldes Maurice Zaoui Annette K. Larsen Michèle Sabbah
author_sort	Nathalie Ferrand
title	WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity
title_short	WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity
title_full	WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity
title_fullStr	WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity
title_full_unstemmed	WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity
title_sort	wisp1/ccn4 inhibits adipocyte differentiation through repression of pparγ activity
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5b0ca59d5a4540bd99b82b8a5908c4f0
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WISP1/CCN4 inhibits adipocyte differentiation through repression of PPARγ activity

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