PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression

Publication date: 19 September 2017
Source:Cell Reports, Volume 20, Issue 12
Author(s): Irfan J. Lodhi, John M. Dean, Anyuan He, Hongsuk Park, Min Tan, Chu Feng, Haowei Song, Fong-Fu Hsu, Clay F. Semenkovich
How the nuclear receptor PPARγ 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 PPARγ 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-β1, a nuclear import factor, and knockdown of PexRAP in adipocytes reduced the levels of nuclear phospholipids. PexRAP also interacts with PPARγ, as well as PRDM16, a critical transcriptional regulator of thermogenesis, and disrupts the PRDM16-PPARγ complex, providing a potential mechanism for PexRAP-mediated inhibition of adipocyte browning. These results identify PexRAP as an important regulator of adipose tissue remodeling.

Graphical abstract

Teaser

Lodhi et al. find that the peroxisomal lipid synthetic enzyme PexRAP is also a nuclear protein that suppresses adipose tissue browning. PexRAP interacts with PPARγ and PRDM16 and inhibits PRDM16-mediated thermogenic gene expression.


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