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PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression

Authors: Lodhi, Irfan J; Dean, John M; He, Anyuan; Park, Hongsuk; Tan, Min; Feng, Chu; Song, Haowei; +2 Authors

PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression

Abstract

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.

Country
United States
Keywords

adipocyte browning, obesity, UCP1, PPARγ, Transcription, Genetic, QH301-705.5, PRDM16, Subcutaneous Fat, Adipose Tissue, Brown, Adipocytes, Animals, Biology (General), Cell Nucleus, Mice, Knockout, Base Sequence, Gene Expression Profiling, Thermogenesis, adipose tissue, DNA-Binding Proteins, Mice, Inbred C57BL, PPAR gamma, Protein Transport, Gene Expression Regulation, Isotope Labeling, beige fat, Protein Binding, Sugar Alcohol Dehydrogenases, Transcription Factors

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    popularity
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    Top 10%
    influence
    This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
    Top 10%
    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 10%
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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
38
Top 10%
Top 10%
Top 10%
gold