University of Pennsylvania, Philadelphia, 19104, USA.
Cell Metab. 2010 Jan;11(1):77-83. doi: 10.1016/j.cmet.2009.10.009.
Medial nucleus tractus solitarius (mNTS) neurons express leptin receptors (LepRs), and intra-mNTS delivery of leptin reduces food intake and body weight. Here, the contribution of endogenous LepR signaling in mNTS neurons to energy balance control was examined. Knockdown of LepR in mNTS and area postrema (AP) neurons of rats (LepRKD) via adeno-associated virus short hairpin RNA-interference (AAV-shRNAi) resulted in significant hyperphagia for chow, high-fat, and sucrose diets, yielding increased body weight and adiposity. The chronic hyperphagia of mNTS/AP LepRKD rats is likely mediated by a reduction in leptin potentiation of gastrointestinal satiation signaling, as LepRKD rats showed decreased sensitivity to the intake-reducing effects of cholecystokinin. LepRKD rats showed increased basal AMP-kinase activity in mNTS/AP micropunches, and pharmacological data suggest that this increase provides a likely mechanism for their chronic hyperphagia. Overall these findings demonstrate that LepRs in mNTS and AP neurons are required for normal energy balance control.
孤束核（mNTS）神经元表达瘦素受体（LepR），mNTS 内注射瘦素可减少食物摄入和体重。本研究旨在探讨 mNTS 神经元内源性 LepR 信号对能量平衡控制的作用。利用腺相关病毒短发夹 RNA 干扰（AAV-shRNAi）技术在大鼠的 mNTS 和后穹窿（AP）神经元中敲低 LepR，导致大鼠对标准饲料、高脂肪饲料和蔗糖饲料的摄食量显著增加，体重和肥胖程度增加。mNTS/AP LepRKD 大鼠的慢性多食可能是通过降低瘦素对胃肠饱食信号的增强作用介导的，因为 LepRKD 大鼠对胆囊收缩素降低摄食的作用敏感性降低。LepRKD 大鼠的 mNTS/AP 微穿刺物中 AMP 激酶活性基础水平升高，药理学数据表明，这种增加可能为其慢性多食提供了一种机制。综上所述，这些发现表明，mNTS 和 AP 神经元中的 LepR 对于正常的能量平衡控制是必需的。
