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The Anti-Adipogenic Potential of COUP-TFII Is Mediated by Downregulation of the Notch Target Gene Hey1.

Scroyen I, Bauters D, Vranckx C, Lijnen HR - PLoS ONE (2015)

Bottom Line: It has not conclusively been established, however, whether its role is pro- or anti-adipogenic.Gene silencing of Coup-tfII in 3T3-F442A preadipocytes resulted in enhanced differentiation into mature adipocytes.A functional role of Hey1 was confirmed by gene silencing in 3T3-F442A preadipocytes, resulting in impaired differentiation.

View Article: PubMed Central - PubMed

Affiliation: KU Leuven, University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000, Leuven, Belgium.

ABSTRACT

Background: Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) belongs to the steroid/thyroid hormone receptor superfamily and may contribute to the pathogenesis of obesity. It has not conclusively been established, however, whether its role is pro- or anti-adipogenic.

Methods and results: Gene silencing of Coup-tfII in 3T3-F442A preadipocytes resulted in enhanced differentiation into mature adipocytes. This was associated with upregulation of the Notch signaling target gene Hey1. A functional role of Hey1 was confirmed by gene silencing in 3T3-F442A preadipocytes, resulting in impaired differentiation. In vivo, de novo fat pad formation in NUDE mice was significantly stimulated following injection of preadipocytes with Coup-tfII gene silencing, but impaired with Hey1 gene silencing. Moreover, expression of Coup-tfII was lower and that of Hey1 higher in isolated adipocytes of obese as compared to lean adipose tissue.

Conclusions: These in vitro and in vivo data support an anti-adipogenic role of COUP-TFII via downregulating the Notch signaling target gene Hey1.

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Related in: MedlinePlus

Expression of Coup-tfII and Hey1 in adipose tissue and isolated cell fractions.Expression of Coup-tfII (A) or Hey1 (B) in gonadal (GN) and subcutaneous (SC) adipose tissues, as well as in isolated adipocytes and stromal vascular fractions (SVF) and in microvascular endothelial cells (MEC) derived from SC and GN adipose tissues obtained from obese mice, is shown relative to samples from lean mice (dotted line). Data are means ± SEM of at least 4 samples; * p < 0.05, ** p < 0.01, *** p < 0.001.
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pone.0145608.g005: Expression of Coup-tfII and Hey1 in adipose tissue and isolated cell fractions.Expression of Coup-tfII (A) or Hey1 (B) in gonadal (GN) and subcutaneous (SC) adipose tissues, as well as in isolated adipocytes and stromal vascular fractions (SVF) and in microvascular endothelial cells (MEC) derived from SC and GN adipose tissues obtained from obese mice, is shown relative to samples from lean mice (dotted line). Data are means ± SEM of at least 4 samples; * p < 0.05, ** p < 0.01, *** p < 0.001.

Mentions: To evaluate Coup-tfII and Hey1 expression in adipose tissue and isolated adipocytes during development of obesity, male C57BL6/N mice, from the age of 5 weeks on, were kept on SFD or HFD for 15 weeks. Coup-tfII expression in GN and SC adipose tissue was lower upon HFD as compared to SFD feeding (Fig 5A). A strong negative correlation was observed between Coup-tfII expression and the GN (r = -0.81; p = 0.002) or SC (r = -0.77; p = 0.003) adipose tissue mass. However, Hey1 expression was only slightly increased in GN fat upon HFD feeding (Fig 5B). In isolated adipocytes from SC or GN fat of obese mice, expression of Coup-tfII was lower as compared to those from lean mice (Fig 5A), whereas expression of Hey1 was slightly but not significantly higher (p = 0.07 or p = 0.09 for SC or GN) (Fig 5B). In addition, relative expression of Coup-tfII was also decreased in the SVF from obese SC or GN adipose tissues, whereas Hey1 expression in SVF did not differ between obese and lean mice (Fig 5A and 5B). Purity of isolated adipocytes and SVF was confirmed by on the expression of the adipocyte specific marker adiponectin and the macrophage marker F4/80 (data not shown).


The Anti-Adipogenic Potential of COUP-TFII Is Mediated by Downregulation of the Notch Target Gene Hey1.

Scroyen I, Bauters D, Vranckx C, Lijnen HR - PLoS ONE (2015)

Expression of Coup-tfII and Hey1 in adipose tissue and isolated cell fractions.Expression of Coup-tfII (A) or Hey1 (B) in gonadal (GN) and subcutaneous (SC) adipose tissues, as well as in isolated adipocytes and stromal vascular fractions (SVF) and in microvascular endothelial cells (MEC) derived from SC and GN adipose tissues obtained from obese mice, is shown relative to samples from lean mice (dotted line). Data are means ± SEM of at least 4 samples; * p < 0.05, ** p < 0.01, *** p < 0.001.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4697848&req=5

pone.0145608.g005: Expression of Coup-tfII and Hey1 in adipose tissue and isolated cell fractions.Expression of Coup-tfII (A) or Hey1 (B) in gonadal (GN) and subcutaneous (SC) adipose tissues, as well as in isolated adipocytes and stromal vascular fractions (SVF) and in microvascular endothelial cells (MEC) derived from SC and GN adipose tissues obtained from obese mice, is shown relative to samples from lean mice (dotted line). Data are means ± SEM of at least 4 samples; * p < 0.05, ** p < 0.01, *** p < 0.001.
Mentions: To evaluate Coup-tfII and Hey1 expression in adipose tissue and isolated adipocytes during development of obesity, male C57BL6/N mice, from the age of 5 weeks on, were kept on SFD or HFD for 15 weeks. Coup-tfII expression in GN and SC adipose tissue was lower upon HFD as compared to SFD feeding (Fig 5A). A strong negative correlation was observed between Coup-tfII expression and the GN (r = -0.81; p = 0.002) or SC (r = -0.77; p = 0.003) adipose tissue mass. However, Hey1 expression was only slightly increased in GN fat upon HFD feeding (Fig 5B). In isolated adipocytes from SC or GN fat of obese mice, expression of Coup-tfII was lower as compared to those from lean mice (Fig 5A), whereas expression of Hey1 was slightly but not significantly higher (p = 0.07 or p = 0.09 for SC or GN) (Fig 5B). In addition, relative expression of Coup-tfII was also decreased in the SVF from obese SC or GN adipose tissues, whereas Hey1 expression in SVF did not differ between obese and lean mice (Fig 5A and 5B). Purity of isolated adipocytes and SVF was confirmed by on the expression of the adipocyte specific marker adiponectin and the macrophage marker F4/80 (data not shown).

Bottom Line: It has not conclusively been established, however, whether its role is pro- or anti-adipogenic.Gene silencing of Coup-tfII in 3T3-F442A preadipocytes resulted in enhanced differentiation into mature adipocytes.A functional role of Hey1 was confirmed by gene silencing in 3T3-F442A preadipocytes, resulting in impaired differentiation.

View Article: PubMed Central - PubMed

Affiliation: KU Leuven, University of Leuven, Department of Cardiovascular Sciences, Center for Molecular and Vascular Biology, B-3000, Leuven, Belgium.

ABSTRACT

Background: Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) belongs to the steroid/thyroid hormone receptor superfamily and may contribute to the pathogenesis of obesity. It has not conclusively been established, however, whether its role is pro- or anti-adipogenic.

Methods and results: Gene silencing of Coup-tfII in 3T3-F442A preadipocytes resulted in enhanced differentiation into mature adipocytes. This was associated with upregulation of the Notch signaling target gene Hey1. A functional role of Hey1 was confirmed by gene silencing in 3T3-F442A preadipocytes, resulting in impaired differentiation. In vivo, de novo fat pad formation in NUDE mice was significantly stimulated following injection of preadipocytes with Coup-tfII gene silencing, but impaired with Hey1 gene silencing. Moreover, expression of Coup-tfII was lower and that of Hey1 higher in isolated adipocytes of obese as compared to lean adipose tissue.

Conclusions: These in vitro and in vivo data support an anti-adipogenic role of COUP-TFII via downregulating the Notch signaling target gene Hey1.

Show MeSH
Related in: MedlinePlus