IEX-1 deficiency induces browning of white adipose tissue and resists diet-induced obesity
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Shahid-2016-IEX-1 deficiency.pdf
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Author(s)
Shahid, Mohd
Javed, Ammar A.
Chandra, David
Ramsey, Haley E.
Shah, Dilip
Khan, Mohammed F.
Zhao, Liping
Wu, Mei X
Date Issued
April 2016
Journal
Scientific Reports
Citation
Shahid, Mohd et al. “IEX-1 Deficiency Induces Browning of White Adipose Tissue and Resists Diet-Induced Obesity.” Scientific Reports 6 (2016): 24135.
Version
Final published version
Abstract
Chronic inflammation plays a crucial role in the pathogenesis of obesity and insulin resistance. However, the primary mediators that affect energy homeostasis remain ill defined. Here, we report an unexpected role for immediate early response gene X-1 (IEX-1), a downstream target of NF-κB, in energy metabolism. We found that IEX-1 expression was highly induced in white adipose tissue (WAT) in both epidydmal and subcutaneous depots but not in interscapular brown adipose tissue (BAT) in mice fed a high fat diet (HFD). Null mutation of IEX-1 protected mice against HFD-induced adipose and hepatic inflammation, hepatic steatosis, and insulin resistance. Unexpectedly, IEX-1 knockout (IEX-1[superscript −/−]) mice gained markedly less weight on HFD for 20 weeks as compared to wild-type (WT) littermates (37 ± 3 versus 48 ± 2 gm) due to increased energy expenditure. Mechanistically, we showed that IEX-1 deficiency induced browning and activated thermogenic genes program in WAT but not in BAT by promoting alternative activation of adipose macrophages. Consequently, IEX-1[superscript −/−] mice exhibited enhanced thermogenesis (24 ± 0.1 versus 22 ± 0.1 kcal/hour/kg in WT mice) explaining increased energy expenditure and lean phenotype in these mice. In conclusion, the present study suggests that IEX-1 is a novel physiological regulator of energy homeostasis via its action in WAT.
MIT Department
Harvard University--MIT Division of Health Sciences and Technology
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DOI of Published Version
https://doi.org/10.1038/srep24135
