能与肥胖相抗衡的有效手段少之又少，而鉴别潜在的治疗靶点需要对控制能量平衡的机制有一个深刻的认识。近日，美国密歇根大学和洛克菲勒大学的研究人员发现，瘦素可通过下丘脑中表达一氧化氮合成酶-1（NOS1，nitric oxide synthase 1）的神经元发挥其控制能量平衡的作用。
瘦素是脂肪细胞分泌的一种激素，大脑中的多种神经元可表达瘦素受体，可表达NOS1的神经元占所有有瘦素受体的神经元的20%。若将表达NOS1的神经元的瘦素受体敲除，小鼠就会食欲过盛、肥胖，且能量消耗降低，合并发生高血糖症。而这些敲除NOS1的神经元的分泌功能只受到轻微影响。
研究结果表明，下丘脑中表达NOS1的含瘦素受体的神经元在瘦素调节的能量平衡中发挥关键作用。下一步的工作将是研究这些神经元的作用机制，进而寻找肥胖及相关疾病的的治疗靶点。（生物谷Bioon.com）
doi:10.1038/nm.2724
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Leptin action through hypothalamic nitric oxide synthase-1–expressing neurons controls energy balance
Rebecca L Leshan,1, 2, 4, 5 Megan Greenwald-Yarnell,1, 3, 5 Christa M Patterson,1 Ian E Gonzalez1 & Martin G Myers Jr1, 2, 3
Few effective measures exist to combat the worldwide obesity epidemic1, and the identification of potential therapeutic targets requires a deeper understanding of the mechanisms that control energy balance. Leptin, an adipocyte-derived hormone that signals the long-term status of bodily energy stores, acts through multiple types of leptin receptor long isoform (LepRb)-expressing neurons (called here LepRb neurons) in the brain to control feeding, energy expenditure and endocrine function2, 3, 4. The modest contributions to energy balance that are attributable to leptin action in many LepRb populations5, 6, 7, 8, 9 suggest that other previously unidentified hypothalamic LepRb neurons have key roles in energy balance. Here we examine the role of LepRb in neuronal nitric oxide synthase (NOS1)-expressing LebRb (LepRbNOS1) neurons that comprise approximately 20% of the total hypothalamic LepRb neurons. Nos1cre-mediated genetic ablation of LepRb (LeprNos1KO) in mice produces hyperphagic obesity, decreased energy expenditure and hyperglycemia approaching that seen in whole-body LepRb-null mice. In contrast, the endocrine functions in LeprNos1KO mice are only modestly affected by the genetic ablation of LepRb in these neurons. Thus, hypothalamic LepRbNOS1 neurons are a key site of action of the leptin-mediated control of systemic energy balance.
