PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing
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PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing. / Kissig, Megan; Ishibashi, Jeff; Harms, Matthew J; Lim, Hee-Woong; Stine, Rachel R; Won, Kyoung-Jae; Seale, Patrick.
In: E M B O Journal, Vol. 36, No. 11, 01.06.2017, p. 1528-1542.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing
AU - Kissig, Megan
AU - Ishibashi, Jeff
AU - Harms, Matthew J
AU - Lim, Hee-Woong
AU - Stine, Rachel R
AU - Won, Kyoung-Jae
AU - Seale, Patrick
N1 - © 2017 The Authors.
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression. Prdm16-deficient adipose displays an exaggerated response to type I IFN, including higher STAT1 levels and reduced mitochondrial gene expression. Mechanistically, PRDM16 represses ISGs through binding to promoter regions of these genes and blocking the activating function of IFN regulatory factor 1 (IRF1). Together, these data indicate that PRDM16 diminishes responsiveness to type I IFN in adipose cells to promote thermogenic and mitochondrial function.
AB - Brown adipose has the potential to counteract obesity, and thus, identifying signaling pathways that regulate the activity of this tissue is of great clinical interest. PRDM16 is a transcription factor that activates brown fat-specific genes while repressing white fat and muscle-specific genes in adipocytes. Whether PRDM16 also controls other gene programs to regulate adipocyte function was unclear. Here, we identify a novel role for PRDM16 in suppressing type I interferon (IFN)-stimulated genes (ISGs), including Stat1, in adipocytes in vitro and in vivo Ectopic activation of type I IFN signaling in brown adipocytes induces mitochondrial dysfunction and reduces uncoupling protein 1 (UCP1) expression. Prdm16-deficient adipose displays an exaggerated response to type I IFN, including higher STAT1 levels and reduced mitochondrial gene expression. Mechanistically, PRDM16 represses ISGs through binding to promoter regions of these genes and blocking the activating function of IFN regulatory factor 1 (IRF1). Together, these data indicate that PRDM16 diminishes responsiveness to type I IFN in adipose cells to promote thermogenic and mitochondrial function.
KW - Adipocytes/physiology
KW - Animals
KW - DNA-Binding Proteins/metabolism
KW - Gene Expression Regulation
KW - Interferon Regulatory Factor-1/antagonists & inhibitors
KW - Interferon Type I/metabolism
KW - Mice
KW - Mitochondria/metabolism
KW - STAT1 Transcription Factor/antagonists & inhibitors
KW - Thermogenesis
KW - Transcription Factors/metabolism
KW - Uncoupling Protein 1/metabolism
U2 - 10.15252/embj.201695588
DO - 10.15252/embj.201695588
M3 - Journal article
C2 - 28408438
VL - 36
SP - 1528
EP - 1542
JO - E M B O Journal
JF - E M B O Journal
SN - 0261-4189
IS - 11
ER -
ID: 199325937