Previous studies indicate that IL-17A plays an important role in mediating the intestinal microbiota and systemic metabolic functions. However, it is not known where IL-17RA signaling occurs to mediate these effects. To investigate this question, we used intestinal epithelial–specific (Il17ra^ΔIEC) and liver-specific (Il17ra^ΔLiver) IL-17RA knockout mice as well as littermate control mice. Our results indicate that intestinal IL-17RA signaling helps mediate systemic metabolic functions upon exposure to prolonged high-fat diet. Il17ra^ΔIEC mice display impaired glucose metabolism, altered hormone and adipokine levels, increased visceral adiposity, and greater hepatic lipid deposition when compared with their littermate controls. We show that IL-17RA–driven changes in microbiota composition are responsible for regulating systemic glucose metabolism. Altogether, our data elucidate the importance of intestinal IL-17RA signaling in regulating high-fat diet–mediated systemic glucose and lipid metabolism.

先前的研究表明，IL-17A 在介导肠道微生物群和全身代谢功能中起重要作用。然而，尚不清楚 IL-17RA 信号在何处发生以介导这些作用。为了研究这个问题，我们使用了肠上皮特异性 ( Il17ra ^{Δ IEC} ) 和肝脏特异性 ( Il17ra ^ΔLiver ) IL-17RA 敲除小鼠以及同窝对照小鼠。我们的研究结果表明，肠道 IL-17RA 信号有助于在长时间暴露于高脂肪饮食后介导全身代谢功能。Il17ra ^{Δ IEC}与同窝小鼠相比，小鼠表现出葡萄糖代谢受损、激素和脂肪因子水平改变、内脏肥胖增加和肝脏脂质沉积增加。我们表明，IL-17RA 驱动的微生物群组成变化是调节全身葡萄糖代谢的原因。总之，我们的数据阐明了肠道 IL-17RA 信号传导在调节高脂饮食介导的全身葡萄糖和脂质代谢中的重要性。