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Manju Kumari, … , Rasheed Ahmad, Evan D. Rosen
Published July 11, 2016
Citation Information: J Clin Invest. 2016;126(8):2839-2854. https://doi.org/10.1172/JCI86080.
Citation Information: J Clin Invest. 2016;126(8):2839-2854. https://doi.org/10.1172/JCI86080.
Abstract
The chronic inflammatory state that accompanies obesity is a major contributor to insulin resistance and other dysfunctional adaptations in adipose tissue. Cellular and secreted factors promote the inflammatory milieu of obesity, but the transcriptional pathways that drive these processes are not well described. Although the canonical inflammatory transcription factor NF-κB is considered to be the major driver of adipocyte inflammation, members of the interferon regulatory factor (IRF) family may also play a role in this process. Here, we determined that IRF3 expression is upregulated in the adipocytes of obese mice and humans. Signaling through TLR3 and TLR4, which lie upstream of IRF3, induced insulin resistance in murine adipocytes, while IRF3 knockdown prevented insulin resistance. Furthermore, improved insulin sensitivity in IRF3-deficient mice was associated with reductions in intra-adipose and systemic inflammation in the high fat–fed state, enhanced browning of subcutaneous fat, and increased adipose expression of GLUT4. Taken together, the data indicate that IRF3 is a major transcriptional regulator of adipose inflammation and is involved in maintaining systemic glucose and energy homeostasis.
Authors
Manju Kumari, Xun Wang, Louise Lantier, Anna Lyubetskaya, Jun Eguchi, Sona Kang, Danielle Tenen, Hyun Cheol Roh, Xingxing Kong, Lawrence Kazak, Rasheed Ahmad, Evan D. Rosen
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Citations to this article (108)
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YM Lee, Y Yoon, H Yoon, HM Park, S Song, KJ Yeum |
Nutrients | 2017 |
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Simultaneous Transcriptional and Epigenomic Profiling from Specific Cell Types within Heterogeneous Tissues In Vivo
HC Roh, LT Tsai, A Lyubetskaya, D Tenen, M Kumari, ED Rosen |
Cell Reports | 2017 |
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A new link between innate immunity and hepatic metabolism: attractive unknown place to visit
H Fukui |
Hepatobiliary surgery and nutrition | 2017 |
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UCP1 deficiency causes brown fat respiratory chain depletion and sensitizes mitochondria to calcium overload-induced dysfunction
L Kazak, ET Chouchani, IG Stavrovskaya, GZ Lu, MP Jedrychowski, DF Egan, M Kumari, X Kong, BK Erickson, J Szpyt, ED Rosen, MP Murphy, BS Kristal, SP Gygi, BM Spiegelman |
Proceedings of the National Academy of Sciences | 2017 |
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Perilla frutescens Extracts Protects against Dextran Sulfate Sodium-Induced Murine Colitis: NF-κB, STAT3, and Nrf2 as Putative Targets
DD Park, HW Yum, X Zhong, SH Kim, SH Kim, DH Kim, SJ Kim, HK Na, A Sato, T Miura, YJ Surh |
Frontiers in pharmacology | 2017 |
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Swine IRF3/IRF7 attenuates inflammatory responses through TLR4 signaling pathway
PG Chen, YJ Guan, GM Zha, XQ Jiao, HS Zhu, CY Zhang, YY Wang, HP Li |
Oncotarget | 2017 |
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Metabolic Vascular Syndrome: New Insights into a Multidimensional Network of Risk Factors and Diseases
GH Scholz, M Hanefeld |
Viszeralmedizin | 2016 |
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