Abstract
BackgroundChicken 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 ResultsGene 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.ConclusionsThese in vitro and in vivo data support an anti-adipogenic role of COUP-TFII via downregulating the Notch signaling target gene Hey1.
Highlights
Over the last decades obesity and its consequences worldwide have become a major health problem
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
Summary
Over the last decades obesity and its consequences worldwide have become a major health problem. Coup-tfII is expressed in adipocytes as well as in the vascular compartment of mainly white adipose tissue, but recent reports on its role in adipogenesis have been contradictory [2, 4, 5]. Coup-tfII expression decreases during differentiation of preadipocytes and its overexpression impairs adipogenesis by repressing the expression of pro-adipogenic factors in adipocytes [5]. Reduced adipose tissue mass and improved glucose homeostasis were shown in heterozygous COUP-TFII mice as compared to wild-type (WT) mice [2]. It is not conclusively established whether COUP-TFII has a pro- or anti-adipogenic potential.
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