Abstract：
:Signaling cascades during adipogenesis culminate in the expression of two essential adipogenic factors, PPARgamma and C/EBPalpha. Here we demonstrate that the IRE1alpha-XBP1 pathway, the most conserved branch of the unfolded protein response (UPR), is indispensable for adipogenesis. Indeed, XBP1-deficient mouse embryonic fibroblasts and 3T3-L1 cells with XBP1 or IRE1alpha knockdown exhibit profound defects in adipogenesis. Intriguingly, C/EBPbeta, a key early adipogenic factor, induces Xbp1 expression by directly binding to its proximal promoter region. Subsequently, XBP1 binds to the promoter of Cebpa and activates its gene expression. The posttranscriptional splicing of Xbp1 mRNA by IRE1alpha is required as only the spliced form of XBP1 (XBP1s) rescues the adipogenic defect exhibited by XBP1-deficient cells. Taken together, our data show that the IRE1alpha-XBP1 pathway plays a key role in adipocyte differentiation by acting as a critical regulator of the morphological and functional transformations during adipogenesis.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Sha H,He Y,Chen H,Wang C,Zenno A,Shi H,Yang X,Zhang X,Qi Ldoi
10.1016/j.cmet.2009.04.009subject
Has Abstractpub_date
2009-06-01 00:00:00pages
556-64issue
6eissn
1550-4131issn
1932-7420pii
S1550-4131(09)00121-1journal_volume
9pub_type
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