Neuroscience Division, Garvan Institute of Medical Research, Sydney, Australia.
Otto Loewi Research Center, Pharmacology Section, Medical University of Graz, Graz, Austria.
Elife. 2018 Aug 21;7:e36494. doi: 10.7554/eLife.36494.
Cocaine- and amphetamine-regulated transcript (CART) is widely expressed in the hypothalamus and an important regulator of energy homeostasis; however, the specific contributions of different CART neuronal populations to this process are not known. Here, we show that depolarization of mouse arcuate nucleus (Arc) CART neurons via DREADD technology decreases energy expenditure and physical activity, while it exerts the opposite effects in CART neurons in the lateral hypothalamus (LHA). Importantly, when stimulating these neuronal populations in the absence of CART, the effects were attenuated. In contrast, while activation of CART neurons in the LHA stimulated feeding in the presence of CART, endogenous CART inhibited food intake in response to Arc CART neuron activation. Taken together, these results demonstrate anorexigenic but anabolic effects of CART upon Arc neuron activation, and orexigenic but catabolic effects upon LHA-neuron activation, highlighting the complex and nuclei-specific functions of CART in controlling feeding and energy homeostasis.
可卡因和苯丙胺调节转录物（CART）广泛表达于下丘脑，是能量平衡的重要调节因子；然而，不同 CART 神经元群体对这一过程的具体贡献尚不清楚。在这里，我们通过 DREADD 技术发现，激活小鼠弓状核（Arc）的 CART 神经元会降低能量消耗和身体活动，而在外侧下丘脑（LHA）的 CART 神经元则会产生相反的效果。重要的是，当在不存在 CART 的情况下刺激这些神经元群体时，效果会减弱。相比之下，虽然 LHA 中的 CART 神经元的激活会刺激 CART 存在时的进食，但内源性 CART 会抑制对 Arc CART 神经元激活的食物摄入。总之，这些结果表明 CART 对 Arc 神经元激活具有厌食但合成代谢的作用，而对 LHA 神经元激活具有摄食但分解代谢的作用，突出了 CART 在控制摄食和能量平衡方面的复杂和核特异性功能。
