能與肥胖相抗衡的有效手段少之又少,，而鑒別潛在的治療靶點(diǎn)需要對(duì)控制能量平衡的機(jī)制有一個(gè)深刻的認(rèn)識(shí),。近日，美國(guó)密歇根大學(xué)和洛克菲勒大學(xué)的研究人員發(fā)現(xiàn),，瘦素可通過(guò)下丘腦中表達(dá)一氧化氮合成酶-1（NOS1,，nitric oxide synthase 1）的神經(jīng)元發(fā)揮其控制能量平衡的作用。
瘦素是脂肪細(xì)胞分泌的一種激素,，大腦中的多種神經(jīng)元可表達(dá)瘦素受體,，可表達(dá)NOS1的神經(jīng)元占所有有瘦素受體的神經(jīng)元的20%。若將表達(dá)NOS1的神經(jīng)元的瘦素受體敲除,，小鼠就會(huì)食欲過(guò)盛,、肥胖，且能量消耗降低,，合并發(fā)生高血糖癥,。而這些敲除NOS1的神經(jīng)元的分泌功能只受到輕微影響。
研究結(jié)果表明,，下丘腦中表達(dá)NOS1的含瘦素受體的神經(jīng)元在瘦素調(diào)節(jié)的能量平衡中發(fā)揮關(guān)鍵作用,。下一步的工作將是研究這些神經(jīng)元的作用機(jī)制，進(jìn)而尋找肥胖及相關(guān)疾病的的治療靶點(diǎn),。（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.
