Abstract：
The central leptin signaling system has been found to facilitate breathing and is linked to obesity-related hypoventilation. Activation of leptin signaling in the nucleus tractus solitarii (NTS) and retrotrapezoid nucleus (RTN) enhances respiratory drive. In this study, we investigated how medullary leptin signaling contributes to hypoventilation and whether respective deletion of SOCS3 in the NTS and RTN could mitigate hypoventilation in diet-induced obesity (DIO) male mice. Our findings revealed a decrease in the number of CO2-activated NTS neurons and downregulation of acid-sensing ion channels in DIO mice compared to lean control mice. Moreover, NTS leptin signaling was disrupted, as evidenced by the downregulation of phosphorylated STAT3 and the upregulation of SOCS3 in DIO mice. Importantly, deleting SOCS3 in the NTS and RTN significantly improved the diminished hypercapnic ventilatory response in DIO mice. In conclusion, our study suggests that disrupted medullary leptin signaling contributes to obesity-related hypoventilation, and inhibiting the upregulated SOCS3 in the NTS and RTN can alleviate this condition.
摘要：
已发现中枢瘦素信号系统促进呼吸，并与肥胖相关的通气不足有关。孤束核（NTS）和后梯形核（RTN）中瘦素信号的激活增强了呼吸驱动。在这项研究中,我们调查了髓质瘦素信号如何导致通气不足,以及NTS和RTN中SOCS3的缺失是否可以减轻饮食诱导的肥胖(DIO)雄性小鼠的通气不足.我们的发现表明，与瘦对照小鼠相比，DIO小鼠中CO2激活的NTS神经元数量减少，酸感应离子通道下调。此外，NTS瘦素信号被破坏,正如DIO小鼠中磷酸化STAT3的下调和SOCS3的上调所证明的那样。重要的是,在NTS和RTN中删除SOCS3可显着改善DIO小鼠的高碳酸血症通气反应减弱。总之,我们的研究表明，受损的髓质瘦素信号有助于肥胖相关的低通气，抑制NTS和RTN中上调的SOCS3可以缓解这种情况。
