Prostaglandin F2alpha inhibits adipogenesis via an autocrine-mediated interleukin-11/glycoprotein 130/STAT1-dependent signaling cascade Journal Article

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Authors: Annamalai, D.; Clipstone, N. A.
Article Title: Prostaglandin F2alpha inhibits adipogenesis via an autocrine-mediated interleukin-11/glycoprotein 130/STAT1-dependent signaling cascade
Abstract: Prostaglandin F2alpha (PGF2alpha) is a potent inhibitor of adipocyte differentiation in vitro, that has also recently been implicated in the regulation of the adipogenic process in vivo, by opposing adipose tissue accretion and the subsequent development of obesity and its attendant metabolic consequences. In previous studies, we have demonstrated that PGF2alpha inhibits adipocyte differentiation by means of a calcium-dependent signaling pathway that is critically dependent upon the activity of the calcineurin phosphatase. In the current study, we have now extended these findings to further elucidate the mechanism by which the PGF2alpha/calcineurin-pathway inhibits the adipogenic process. We now report that the IL-11 cytokine, a member of the gp130 cytokine co-receptor-related family, is a downstream transcriptional target of this pathway in 3T3-L1 preadipocytes and is actively secreted in differentiating cells in response to PGF2alpha stimulation. Using a combined shRNA and dominant-negative receptor mutant approach, we provide evidence that IL-11/gp130-signaling is required to mediate the inhibitory effects of PGF2alpha on adipogenesis. Moreover, by taking advantage of a well-characterized panel of chimeric gp130 mutant receptors, we demonstrate that gp130 signaling is sufficient to inhibit adipocyte differentiation and specifically requires the activation of the STAT1 transcription factor. Conversely, we find that depleting endogenous STAT1 levels rescues adipogenesis in the presence of both IL-11/gp130 signaling and PGF2alpha. Collectively, our findings support a model in which PGF2alpha inhibits adipocyte differentiation by means of an IL-11 mediated autocrine negative feedback loop, that acts via gp130 to block adipogenesis through the essential actions of the STAT1 transcription factor.
Journal Title: Journal of cellular biochemistry
Volume: 115
Issue: 7
ISSN: 1097-4644; 0730-2312
Publisher: Wiley Periodicals, Inc  
Journal Place: United States
Date Published: 2014
Start Page: 1308
End Page: 1321
Language: eng
DOI/URL:

10.1002/jcb.24785
Notes: CI: (c) 2014; JID: 8205768; OTO: NOTNLM; 2013/12/06 [received]; 2014/02/06 [accepted]; ppublish