PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing

Research output: Contribution to journalJournal articleResearchpeer-review

  • Megan Kissig
  • Jeff Ishibashi
  • Matthew J Harms
  • Hee-Woong Lim
  • Rachel R Stine
  • Won, Kyoung Jae
  • Patrick Seale

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.

Original languageEnglish
JournalE M B O Journal
Volume36
Issue number11
Pages (from-to)1528-1542
Number of pages15
ISSN0261-4189
DOIs
Publication statusPublished - 1 Jun 2017
Externally publishedYes

    Research areas

  • Adipocytes/physiology, Animals, DNA-Binding Proteins/metabolism, Gene Expression Regulation, Interferon Regulatory Factor-1/antagonists & inhibitors, Interferon Type I/metabolism, Mice, Mitochondria/metabolism, STAT1 Transcription Factor/antagonists & inhibitors, Thermogenesis, Transcription Factors/metabolism, Uncoupling Protein 1/metabolism

ID: 199325937