Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei Province, China; Functional Laboratory, Experimental Center for Teaching, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Department of Neurobiology, Hebei Medical University, Shijiazhuang, Hebei Province, China.
Brain Res. 2024 Jan 1;1822:148608. doi: 10.1016/j.brainres.2023.148608. Epub 2023 Sep 29.
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 CO-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.
中央瘦素信号系统已被发现有助于呼吸，并与肥胖相关的通气不足有关。孤束核（NTS）和延髓梯形核（RTN）中瘦素信号的激活增强了呼吸驱动。在这项研究中，我们研究了髓质瘦素信号如何导致通气不足，以及 NTS 和 RTN 中 SOCS3 的各自缺失是否可以减轻饮食诱导肥胖（DIO）雄性小鼠的通气不足。我们的研究结果表明，与瘦鼠相比，DIO 小鼠中 CO 激活的 NTS 神经元数量减少，酸敏离子通道下调。此外，DIO 小鼠中 NTS 瘦素信号被破坏，这表现在磷酸化 STAT3 的下调和 SOCS3 的上调。重要的是，在 NTS 和 RTN 中删除 SOCS3 可显著改善 DIO 小鼠减弱的高碳酸血症性通气反应。总之，我们的研究表明，破坏的髓质瘦素信号导致肥胖相关的通气不足，抑制 NTS 和 RTN 中上调的 SOCS3 可以缓解这种情况。
