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Publication : PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression.

First Author  Lodhi IJ Year  2017
Journal  Cell Rep Volume  20
Issue  12 Pages  2766-2774
PubMed ID  28930673 Mgi Jnum  J:251809
Mgi Id  MGI:6103958 Doi  10.1016/j.celrep.2017.08.077
Citation  Lodhi IJ, et al. (2017) PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression. Cell Rep 20(12):2766-2774
abstractText  How the nuclear receptor PPARgamma regulates the development of two functionally distinct types of adipose tissue, brown and white fat, as well as the browning of white fat, remains unclear. Our previous studies suggest that PexRAP, a peroxisomal lipid synthetic enzyme, regulates PPARgamma signaling and white adipogenesis. Here, we show that PexRAP is an inhibitor of brown adipocyte gene expression. PexRAP inactivation promoted adipocyte browning, increased energy expenditure, and decreased adiposity. Identification of PexRAP-interacting proteins suggests that PexRAP function extends beyond its role as a lipid synthetic enzyme. Notably, PexRAP interacts with importin-beta1, a nuclear import factor, and knockdown of PexRAP in adipocytes reduced the levels of nuclear phospholipids. PexRAP also interacts with PPARgamma, as well as PRDM16, a critical transcriptional regulator of thermogenesis, and disrupts the PRDM16-PPARgamma complex, providing a potential mechanism for PexRAP-mediated inhibition of adipocyte browning. These results identify PexRAP as an important regulator of adipose tissue remodeling.
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