Neuropeptide Y (NPY) producing neurons in the arcuate nucleus (Arc) of the hypothalamus are essential to the regulation of food intake and energy homeostasis. Whilst they have classically been thought to co-express agouti-related peptide (AgRP), it is now clear that there is a sub-population of NPY neurons in the Arc that do not. Here, we show that a subset of AgRP-negative, NPY-positive neurons in the Arc also express neurotensin (NTS) and we use an NTS-Cre line to investigate the function of this sub-population of NPY neurons. The lack of NPY in NTS-positive neurons led to a marked reduction in fat mass and bodyweight as well as a significant reduction in food intake in male NPYlox/lox; NTScre/+ mice compared to controls. Despite the reduction in food intake, overall energy expenditure was similar between genotypes due to concomitant reduction in activity in NPYlox/lox; NTScre/+ mice. Furthermore, cortical bone mass was significantly reduced in NPYlox/lox;NTScre/+ mice with no evident alterations in the cancellous bone compartment, likely due to reduced leptin levels as a result of their reduced adiposity. Taken together, these data suggest that the sub-population of Arc NPY neurons expressing NTS are critical for regulating food intake, activity and fat mass but are not directly involved in the control of bone mass.

中文翻译：

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神经降压素神经元中缺乏 NPY 导致瘦表型

下丘脑弓状核 (Arc) 中产生神经肽 Y (NPY) 的神经元对于调节食物摄入和能量稳态至关重要。虽然传统上认为它们与刺鼠相关肽 (AgRP) 共表达，但现在很明显，弧中存在一个 NPY 神经元亚群没有。在这里，我们展示了 Arc 中 AgRP 阴性、NPY 阳性神经元的一个子集也表达神经降压素 (NTS)，我们使用 NTS-Cre 线来研究这个 NPY 神经元亚群的功能。NTS 阳性神经元中 NPY 的缺乏导致男性 NPYlox/lox 的脂肪量和体重显着减少，以及食物摄入量显着减少；NTScre/+ 小鼠与对照相比。尽管减少了食物的摄入量，由于 NPYlox/lox 的活性同时降低，基因型之间的总体能量消耗相似；NTScre/+ 小鼠。此外，NPYlox/lox;NTScre/+ 小鼠的皮质骨量显着降低，松质骨区室没有明显变化，这可能是由于肥胖减少导致瘦素水平降低。总之，这些数据表明，表达 NTS 的 Arc NPY 神经元亚群对调节食物摄入、活动和脂肪量至关重要，但不直接参与骨量的控制。