<i>Dact1</i>, a Nutritionally Regulated Preadipocyte Gene, Controls Adipogenesis by Coordinating the Wnt/β-Catenin Signaling Network

Lagathu, Claire; Christodoulides, Constantinos; Virtue, Sam; Cawthorn, William P.; Franzin, Chiara; Kimber, Wendy A.; Nora, Edoardo Dalla; Campbell, Mark; Medina-Gómez, Gema; Cheyette, Benjamin N.R.; Vidal-Puig, António; Sethi, J.

doi:10.2337/db08-1180

Cited by 92 publications

(89 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In addition, Sfrp5 transcript levels in adipose tissue were shown to correlate with adipocyte size (7). Consistent with this, Sfrp5 expression has been previously shown to be induced by refeeding (11).…”

supporting

confidence: 74%

Lighting the fat furnace without SFRP5

Rauch¹,

Mandrup²

2012

J. Clin. Invest.

View full text Add to dashboard Cite

supporting

confidence: 74%

Lighting the fat furnace without SFRP5

Rauch¹,

Mandrup²

2012

J. Clin. Invest.

View full text Add to dashboard Cite

“…In agreement with this study, we found no changes in circulating SFRP5 levels or in Sfrp5 expression in peripancreatic adipose tissue between CAF-and STD-fed rats (data not shown). Therefore, its implication in metabolic dysfunction remains controversial [34][35][36]. Importantly, our study demonstrates a novel autocrine role for SFRP5 in beta cell proliferation.…”

Section: Discussionmentioning

confidence: 84%

Downregulation of Sfrp5 promotes beta cell proliferation during obesity in the rat

et al. 2013

View full text Add to dashboard Cite

Aims/hypothesis During obesity, the increment in beta cell mass in response to the rising demand for insulin is essential to maintain normal glucose homeostasis. However, the precise cellular and molecular mechanisms involved in beta cell mass plasticity remain poorly understood. The Wnt signalling pathway has been suggested as one possible modulator of beta cell proliferation, which represents the principal process involved in beta cell mass expansion. Here, we sought to determine the mechanisms involved in beta cell mass proliferation using diet-induced obese rats. Methods Wistar rats aged 8 weeks old were fed a standard or cafeteria diet. Global transcriptomic analysis of pancreatic rat islets was performed using microarray analysis. Genetic lossof-function approaches were performed in dispersed primary rat islets and the beta cell line INS1E. Gene expression was measured by real-time PCR, protein levels by immunoblot analysis, proliferation rates by ELISA and apoptosis by flow cytometry. Results Sfrp5, coding for secreted frizzled-related protein 5, is downregulated in the pancreatic islets of cafeteria-diet-fed rats as well as in the pancreatic islets of human obese patients. We demonstrate that silencing Sfrp5 increases beta cell proliferation, which correlates with activation of Wnt signalling and enhanced levels of proliferation markers. In addition, we show that expression of Sfrp5 in beta cells is modulated by IGF binding protein 3 (IGFBP3) secreted from visceral adipose tissue. Conclusions/interpretation Together, these findings reveal an important role for SFRP5 and Wnt signalling in the regulation of beta cell proliferation in obesity.

show abstract

“…Of these, SFRPs have been the most extensively studied in the context of adipose tissue (16,(30)(31)(32). SFRPs have an N-terminal cysteine-rich domain that is homologous to frizzled proteins, the cell surface receptors for WNT ligands; these proteins also have a C-terminal netrin domain of unknown function (29).…”

Section: Introductionmentioning

confidence: 99%

“…In 3T3-L1 preadipocytes, purified recombinant SFRP1 (and SFRP2) or ectopic SFRP1 expression inhibits WNT/β-catenin signaling and stimulates adipogenesis (16,30). Sfrp5 is also induced during 3T3-L1 adipogenesis and is expressed more highly in isolated adipocytes than in stromalvascular cells (31,32,34). Although 3 groups have reported that Sfrp5 is highly induced with genetic and/or diet-induced obesity (31,32,35), another found suppression of Sfrp5 under these conditions (34).…”

Section: Introductionmentioning

confidence: 99%

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

Mori¹,

Prestwich²,

Reid³

et al. 2012

J. Clin. Invest.

Self Cite

144

160

View full text Add to dashboard Cite

Preadipocytes secrete several WNT family proteins that act through autocrine/paracrine mechanisms to inhibit adipogenesis. The activity of WNT ligands is often decreased by secreted frizzled-related proteins (SFRPs). Sfrp5 is strongly induced during adipocyte differentiation and increases in adipocytes during obesity, presumably to counteract WNT signaling. We tested the hypothesis that obesity-induced Sfrp5 expression promotes the development of new adipocytes by inhibiting endogenous suppressors of adipogenesis. As predicted, mice that lack functional SFRP5 were resistant to diet-induced obesity. However, counter to our hypothesis, we found that adipose tissue of SFRP5-deficient mice had similar numbers of adipocytes, but a reduction in large adipocytes. Transplantation of adipose tissue from SFRP5-deficient mice into leptin receptor-deficient mice indicated that the effects of SFRP5 deficiency are tissue-autonomous. Mitochondrial gene expression was increased in adipose tissue and cultured adipocytes from SFRP5-deficient mice. In adipocytes, lack of SFRP5 stimulated oxidative capacity through increased mitochondrial activity, which was mediated in part by PGC1α and mitochondrial transcription factor A. WNT3a also increased oxygen consumption and the expression of mitochondrial genes. Thus, our findings support a model of adipogenesis in which SFRP5 inhibits WNT signaling to suppress oxidative metabolism and stimulate adipocyte growth during obesity.

show abstract

Dact1, a Nutritionally Regulated Preadipocyte Gene, Controls Adipogenesis by Coordinating the Wnt/β-Catenin Signaling Network

Cited by 92 publications

References 30 publications

Lighting the fat furnace without SFRP5

Lighting the fat furnace without SFRP5

Downregulation of Sfrp5 promotes beta cell proliferation during obesity in the rat

Secreted frizzled-related protein 5 suppresses adipocyte mitochondrial metabolism through WNT inhibition

Contact Info

Product

Resources

About