| First Author | Kissig M | Year | 2017 |
| Journal | EMBO J | Volume | 36 |
| Issue | 11 | Pages | 1528-1542 |
| PubMed ID | 28408438 | Mgi Jnum | J:243350 |
| Mgi Id | MGI:5908290 | Doi | 10.15252/embj.201695588 |
| Citation | Kissig M, et al. (2017) PRDM16 represses the type I interferon response in adipocytes to promote mitochondrial and thermogenic programing. EMBO J 36(11):1528-1542 |
| abstractText | 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. |
