| First Author | Hoang AC | Year | 2022 |
| Journal | Nat Metab | Volume | 4 |
| Issue | 12 | Pages | 1684-1696 |
| PubMed ID | 36443525 | Mgi Jnum | J:361020 |
| Mgi Id | MGI:7855107 | Doi | 10.1038/s42255-022-00683-w |
| Citation | Hoang AC, et al. (2022) Mitochondrial RNA stimulates beige adipocyte development in young mice. Nat Metab 4(12):1684-1696 |
| abstractText | Childhood obesity is a serious public health crisis and a critical factor that determines future obesity prevalence. Signals affecting adipocyte development in early postnatal life have a strong potential to trigger childhood obesity; however, these signals are still poorly understood. We show here that mitochondrial (mt)RNA efflux stimulates transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis in adipocytes of young mice and human infants. While cytosolic mtRNA is a potential trigger of the interferon (IFN) response, young adipocytes lack such a response to cytosolic mtRNA due to the suppression of IFN regulatory factor (IRF)7 expression by vitamin D receptor signalling. Adult and obese adipocytes, however, strongly express IRF7 and mount an IFN response to cytosolic mtRNA. In turn, suppressing IRF7 expression in adult adipocytes restores mtRNA-induced mitobiogenesis and thermogenesis and eventually mitigates obesity. Retrograde mitochondrion-to-nucleus signalling by mtRNA is thus a mechanism to evoke thermogenic potential during early adipocyte development and to protect against obesity. |
