CCAAT/Enhancer Binding-Proteins α and β Are Transcriptional Activators of the Brown Fat Uncoupling Protein Gene Promoter

ATF4 regulates lipid metabolism and thermogenesis

“…Levels of serum NE, how- ever, were significantly increased in Atf4 −/− mice, suggesting a possible involvement of the SNS in enhanced UCP1 expression. It has been reported that Ucp1 expression, in response to activation of the SNS, is upregulated by the transcription factors PGC1α and PPARγ [25,26]. Pgc1α and Pparγ expression were also increased in BAT of Atf4 −/− mice, suggesting that the increased UCP1 expression is mediated by PGC1α and PPARγ.…”

“…To investigate the mechanisms of increased UCP1 expression, we examined expression levels of transcription factors that regulate UCP1 gene expression, including PGC1α and PPARγ [25,26]. Expression of Pgc1α and Pparγ was significantly increased in BAT of Atf4 −/− mice compared with Atf4 +/+ mice ( Figure 5G).…”

Insulin-induced Up-regulated Uncoupling Protein-1 Expression Is Mediated by Insulin Receptor Substrate 1 through the Phosphatidylinositol 3-Kinase/Akt Signaling Pathway in Fetal Brown Adipocytes

“…Activity in an IRS-1-dependent Manner-It has been reported that the 5Ј-flanking region of the UCP-1 gene contains C/EBPsregulated sites (37). In fact, previous data from our laboratory indicated that the three canonical C/EBP isoforms (␣, ␤, and ␦) are expressed in brown adipose tissue during late fetal development, with C/EBP␣ positively regulated by insulin (5,14).…”

The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP

“…The genomic organization of the mouse, rat and human UCP1 genes has been analysed in several laboratories [7,8,[130][131][132][133][134][135][136][137][138][139][140][141][142][143][144][145]. The structure of the UCP1 gene is highly conserved in these three species.…”

“…A new co-activator, referred to as PGC-1 (peroxisome gamma co-activator 1), was identified in BAT and skeletal muscle ; this protein co-activates the transcriptional effect of peroxisomeproliferator-activated receptor γ and thyroid-hormone receptors in the UCP1 gene [142]. Other elements present in the proximal region of the UCP1 gene promoter also mediate regulation of UCP1 gene transcription to cAMP, C\EBP (CCAAT-enhancerbinding protein) α, C\EBP β and c-Jun [135,[143][144][145]. Table 3 Linkage or association studies of the human UCP1, UCP2 and UCP2 genes RMR, resting metabolic rate ; BMI, body mass index [ratio between height (m) and square of body weight (kg 2 )].…”