Gsα signalling suppresses PPARγ2 generation and inhibits 3T3L1 adipogenesis

Zhang, Lei ORCID: https://orcid.org/0000-0003-3536-8692, Paddon, Carol Ann, Lewis, Mark David, Grennan-Jones, Fiona Antoinette and Ludgate, Marian Elizabeth 2009. Gsα signalling suppresses PPARγ2 generation and inhibits 3T3L1 adipogenesis. Journal of Endocrinology 202 (2) , pp. 207-215. 10.1677/JOE-09-0099

Full text not available from this repository.

Abstract

Since TSH receptor (TSHR) expression increases during adipogenesis and signals via cAMP/phospho-cAMP-response element binding protein (CREB), reported to be necessary and sufficient for adipogenesis, we hypothesised that TSHR activation would induce preadipocyte differentiation. Retroviral vectors introduced constitutively active TSHR (TSHR*) into 3T3L1 preadipocytes; despite increased cAMP (RIA) and phospho-CREB (western blot) there was no spontaneous adipogenesis (assessed morphologically, using oil red O and QPCR measurement of adipogenesis markers). We speculated that Gβγ signalling may be inhibitory but failed to induce adipogenesis using activated Gsα (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 PPARγ (PPARG as listed in the HUGO database) by phosphorylation but expression of PPARγ1 was reduced and PPARγ2 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 Gsα signalling impedes FOXO1 phosphorylation and thus inhibits PPARγ transcription and the alternative promoter usage required to generate PPARγ2, the fat-specific transcription factor necessary for adipogenesis.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Publisher:	Society for Endocrinology
ISSN:	0022-0795
Last Modified:	20 Oct 2022 08:54
URI:	https://orca.cardiff.ac.uk/id/eprint/30010

Citation Data

Cited 23 times in Scopus. View in Scopus. Powered By Scopus® Data

Actions (repository staff only)

Edit Item