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Cell Rep. 2017 Sep 19;20(12):2766-2774. doi: 10.1016/j.celrep.2017.08.077.

PexRAP Inhibits PRDM16-Mediated Thermogenic Gene Expression.

Author information

1
Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA. Electronic address: ilodhi@wustl.edu.
2
Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA.
3
Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110, USA.
4
Division of Endocrinology, Metabolism & Lipid Research, Washington University School of Medicine, Saint Louis, MO 63110, USA; Division of Biology and Biomedical Sciences, Washington University School of Medicine, Saint Louis, MO 63110, USA; Department of Cell Biology and Physiology, Washington University School of Medicine, Saint Louis, MO 63110, USA.

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.

KEYWORDS:

PPARγ; PRDM16; UCP1; adipocyte browning; adipose tissue; beige fat; obesity

PMID:
28930673
PMCID:
PMC5679740
DOI:
10.1016/j.celrep.2017.08.077
[Indexed for MEDLINE]
Free PMC Article

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