Bassi M, Furuya W I, Menani J V, Colombari D S A, do Carmo J M, da Silva A A, Hall J E, Moreira T S, Wenker I C, Mulkey D K, Colombari E
Department of Physiology and Pathology, School of Dentistry, São Paulo State University (UNESP), Araraquara, SP, Brazil.
Acta Physiol (Oxf). 2014 May;211(1):240-8. doi: 10.1111/apha.12257. Epub 2014 Mar 13.
Leptin, an adipocyte-derived hormone, is suggested to participate in the central control of breathing. We hypothesized that leptin may facilitate ventilatory responses to chemoreflex activation by acting on respiratory nuclei of the ventrolateral medulla. The baseline ventilation and the ventilatory responses to CO2 were evaluated before and after daily injections of leptin into the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) for 3 days in obese leptin-deficient (ob/ob) mice.
Male ob/ob mice (40-45 g, n = 7 per group) received daily microinjections of vehicle or leptin (1 μg per 100 nL) for 3 days into the RTN/pFRG. Respiratory responses to CO2 were measured by whole-body plethysmography.
Unilateral microinjection of leptin into the RTN/pFRG in ob/ob mice increased baseline ventilation (VE ) from 1447 ± 96 to 2405 ± 174 mL min(-1) kg(-1) by increasing tidal volume (VT ) from 6.4 ± 0.4 to 9.1 ± 0.8 mL kg(-1) (P < 0.05). Leptin also enhanced ventilatory responses to 7% CO2 (Δ = 2172 ± 218 mL min(-1) kg(-1) , vs. control: Δ = 1255 ± 105 mL min(-1) kg(-1) ), which was also due to increased VT (Δ = 4.71 ± 0.51 mL kg(-1) , vs. control: Δ = 2.27 ± 0.20 mL kg(-1) ), without changes in respiratory frequency. Leptin treatment into the RTN/pFRG or into the surrounding areas decreased food intake (83 and 70%, respectively), without significantly changing body weight.
The present results suggest that leptin acting in the respiratory nuclei of the ventrolateral medulla improves baseline VE and VT and facilitates respiratory responses to hypercapnia in ob/ob mice.
瘦素是一种脂肪细胞衍生的激素，被认为参与呼吸的中枢控制。我们假设瘦素可能通过作用于延髓腹外侧呼吸核来促进对化学反射激活的通气反应。在肥胖的瘦素缺乏（ob/ob）小鼠中，每日向梯形核后区/面神经旁呼吸组（RTN/pFRG）注射瘦素3天前后，评估基线通气和对二氧化碳的通气反应。
雄性ob/ob小鼠（40 - 45克，每组n = 7）连续3天每日向RTN/pFRG微量注射溶剂或瘦素（每100纳升1微克）。通过全身体积描记法测量对二氧化碳的呼吸反应。
向ob/ob小鼠的RTN/pFRG单侧微量注射瘦素，通过将潮气量（VT）从6.4±0.4毫升/千克增加到9.1±0.8毫升/千克（P < 0.05），使基线通气量（VE）从1447±96增加到2405±174毫升·分钟⁻¹·千克⁻¹。瘦素还增强了对7%二氧化碳的通气反应（Δ = 2172±218毫升·分钟⁻¹·千克⁻¹，对照组：Δ = 1255±105毫升·分钟⁻¹·千克⁻¹），这也是由于VT增加（Δ = 4.71±0.51毫升/千克，对照组：Δ = 2.27±0.20毫升/千克），而呼吸频率无变化。向RTN/pFRG或其周围区域注射瘦素可减少食物摄入量（分别为83%和70%），而体重无显著变化。
目前的结果表明，作用于延髓腹外侧呼吸核的瘦素可改善ob/ob小鼠的基线VE和VT，并促进对高碳酸血症的呼吸反应。
