Nuclear hormone receptor LXRa inhibits adipocyte differentiation of mesenchymal stem cells with Wnt/ XXXX signaling.

@entity28 @entity19 @entity23710 @entity281 @entity12401 @entity209 @entity165
UNASSIGNED: Nuclear hormone receptor liver X receptor-alpha (LXRa) has a vital role in @entity165 homeostasis and is reported to have a role in adipose function and @entity28 although this is controversial. Conversely, mesenchymal stem cells (MSCs) are suggested to be a major source of adipocyte generation. Accordingly, we examined the role of LXRa in adipogenesis of MSCs. Adult @entity19 MSCs (mMSCs) were isolated from wild-type (WT) and @entity23710 -null @entity19 . Using WT mMSCs, we further generated cell lines stably overexpressing GFP-LXRa (mMSC/LXRa/GFP) or GFP alone (mMSC/GFP) by @entity281 . Confluent mMSCs were differentiated into adipocytes by the established protocol. Compared with MSCs isolated from WT @entity19 , MSCs from @entity23710 -null @entity19 showed significantly increased adipogenesis, as determined by lipid droplet accumulation and adipogenesis-related gene expression. Moreover, mMSCs stably overexpressing GFP-LXRa (mMSC/LXRa/GFP) exhibited significantly decreased adipogenesis compared with mMSCs overexpressing GFP alone (mMSC/GFP). Since Wnt/ @entity12401 signaling is reported to inhibit adipogenesis, we further examined it. The @entity23710 -null group showed significantly decreased Wnt expression accompanied by a decrease of cellular @entity12401 (vs WT). The mMSC/LXRa/GFP group exhibited significantly increased Wnt expression accompanied by an increase of cellular @entity12401 (vs mMSC/GFP). These data demonstrate that LXRa has an inhibitory effect on adipogenic differentiation in mMSCs with Wnt/ @entity12401 signaling. These results provide important insights into the pathophysiology of @entity28 and @entity28 -related consequences such as @entity209 and may identify potential therapeutic targets.Laboratory Investigation advance online publication, 23 November 2015; doi:10.1038/labinvest.2015.141.
