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.

儿童肥胖是严重的公共卫生危机，也是决定未来肥胖患病率的关键因素。影响产后早期脂肪细胞发育的信号极有可能引发儿童肥胖；然而，这些信号仍然知之甚少。我们在这里展示线粒体 (mt)RNA 流出刺激核编码基因的转录，用于幼鼠和人类婴儿脂肪细胞中的线粒体生成和产热。虽然胞质 mtRNA 是干扰素 (IFN) 反应的潜在触发因素，但由于维生素 D 受体信号传导抑制了 IFN 调节因子 (IRF)7 的表达，年轻脂肪细胞缺乏对胞质 mtRNA 的这种反应。然而，成人和肥胖脂肪细胞强烈表达 IRF7 并对胞质 mtRNA 产生 IFN 反应。反过来，抑制成人脂肪细胞中的 IRF7 表达可恢复 mtRNA 诱导的线粒体生成和产热作用，并最终减轻肥胖。因此，通过 mtRNA 进行的逆行线粒体到细胞核信号转导是一种在早期脂肪细胞发育过程中激发产热潜能并防止肥胖的机制。