| First Author | Armengol J | Year | 2012 |
| Journal | Biochem J | Volume | 443 |
| Issue | 3 | Pages | 799-810 |
| PubMed ID | 22324440 | Mgi Jnum | J:185479 |
| Mgi Id | MGI:5428830 | Doi | 10.1042/BJ20111714 |
| Citation | Armengol J, et al. (2012) Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPdelta. Biochem J 443(3):799-810 |
| abstractText | Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) alpha-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPdelta activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPdelta knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPdelta in C/EBPalpha-null BAT and high expression of C/EBPdelta in brown pre-adipocytes. Dexamethasone treatment of brown pre-adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPdelta and strongly impaired expression of the thermogenic markers UCP1 and PGC-1alpha [PPARgamma (peroxisome-proliferator-activated receptor gamma) co-activator-alpha]. However, it did not alter normal fat accumulation or expression of non-BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPdelta as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation. |
