Abstract：
Repeated bouts of high-intensity interval training (HIIT) induce an improvement in metabolism via plasticity of melanocortin circuits and attenuated hypothalamic inflammation. HIF-1α, which plays a vital role in hypothalamus-mediated regulation of peripheral metabolism, is enhanced in the hypothalamus by HIIT. This study aimed to investigate the effects of HIIT on hypothalamic HIF-1α expression and peripheral metabolism in obese mice and the underlying molecular mechanisms. By using a high-fat diet (HFD)-induced obesity mouse model, we determined the effect of HIIT on energy balance and the expression of the hypothalamic appetite-regulating neuropeptides, POMC and NPY. Moreover, hypothalamic HIF-1α signaling and its downstream glycolytic enzymes were explored after HIIT intervention. The state of microglia and microglial NF-κB signaling in the hypothalamus were also examined in vivo. In vitro by using an adenovirus carrying shRNA-HIF1β, we explored the impact of HIF-1 signaling on glycolysis and NF-κB inflammatory signaling in BV2 cells. Food intake was suppressed and whole-body metabolism was improved in exercised DIO mice, accompanied by changes in the expression of POMC and NPY. Moreover, total and microglial HIF-1α signaling were obviously attenuated in the hypothalamus, consistent with the decreased levels of glycolytic enzymes. Both HFD-induced microglial activation and hypothalamic NF-κB signaling were significantly suppressed following HIIT in vivo. In BV2 cells, after HIF-1 complex knockdown, glycolysis and NF-κB inflammatory signaling were significantly attenuated. The data indicate that HIIT improves peripheral metabolism probably via attenuated HFD-induced microglial activation and microglial NF-κB signaling in the hypothalamus, which could be mediated by suppressed microglial HIF-1α signaling.
摘要：
高强度间歇训练（HIIT）的反复发作通过黑皮质素回路的可塑性和下丘脑炎症的减轻引起新陈代谢的改善。HIF-1α,在下丘脑介导的外周代谢调节中起着至关重要的作用，通过HIIT增强下丘脑。本研究旨在探讨HIIT对肥胖小鼠下丘脑HIF-1α表达及外周代谢的影响及其分子机制。采用高脂饮食(HFD)诱导的肥胖小鼠模型,我们确定了HIIT对能量平衡和下丘脑食欲调节神经肽表达的影响，POMC和NPY。此外，对HIIT干预后的下丘脑HIF-1α信号及其下游糖酵解酶进行了研究。还在体内检查了下丘脑中的小胶质细胞和小胶质细胞NF-κB信号的状态。通过使用携带shRNA-HIF1β的腺病毒在体外，我们探讨了HIF-1信号对BV2细胞糖酵解和NF-κB炎症信号的影响。在运动的DIO小鼠中，食物摄入受到抑制，全身代谢得到改善，同时伴有POMC和NPY表达的变化。此外，下丘脑HIF-1α总信号和小胶质细胞信号明显减弱，与糖酵解酶水平降低一致。在体内HIIT后，HFD诱导的小胶质细胞活化和下丘脑NF-κB信号传导均被显着抑制。在BV2细胞中，在HIF-1复合物敲除后，糖酵解和NF-κB炎症信号显著减弱。数据表明，HIIT可能通过减弱HFD诱导的下丘脑小胶质细胞活化和小胶质细胞NF-κB信号来改善外周代谢，这可能是由抑制小胶质细胞HIF-1α信号介导的。
