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signalling suppresses PPAR
2 generation and inhibits 3T3L1 adipogenesis
School of Medicine, Centre for Endocrine and Diabetes Sciences, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
(Correspondence should be addressed to M Ludgate; Email: ludgate{at}cf.ac.uk)
This is an Open Access article distributed under the terms of the Society for Endocrinology's Re-use Licence which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
signalling may be inhibitory but failed to induce adipogenesis using activated Gs
(gsp*). Inhibition of phosphodiesterases did not promote adipogenesis in TSHR* or gsp* populations. Furthermore, differentiation induced by adipogenic medium with pioglitazone was reduced in TSHR* and abolished in gsp* expressing 3T3L1 cells. TSHR* and gsp* did not inactivate PPAR
(PPARG as listed in the HUGO database) by phosphorylation but expression of PPAR
1 was reduced and PPAR
2 undetectable in gsp*. FOXO1 phosphorylation (required to inactivate this repressor of adipogenesis) was lowest in gsp* despite the activation of AKT by phosphorylation. PROF is a mediator that facilitates FOXO1 phosphorylation by phospho-Akt. Its transcript levels remained constantly low in the gsp* population. In most measurements, the TSHR* cells were between the gsp* and control 3T3L1 preadipocytes. The enhanced down-regulation of PREF1 (adipogenesis inhibitor) permits retention of some adipogenic potential in the TSHR* population. We conclude that Gs
signalling impedes FOXO1 phosphorylation and thus inhibits PPAR
transcription and the alternative promoter usage required to generate PPAR
2, the fat-specific transcription factor necessary for adipogenesis.
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