Food-induced dopamine signaling in AgRP neurons promotes feeding.
Food-induced dopamine signaling in AgRP neurons promotes feeding.
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DOI：
10.1016/j.celrep.2022.111718
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发表时间：
2022-11-29
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
肥胖合并症，如糖尿病和心血管疾病是紧迫的公共卫生问题。过度消耗卡路里会导致体重增加;然而，过度食物消耗的神经机制却知之甚少。在这里，我们证明，多巴胺受体D1（Drd1）表达的刺豚鼠相关肽/神经肽Y（AgRP/NPY）神经元的弓状下丘脑是需要适当的反应，高脂饮食（HFD）。刺激Drd1和AgRP/NPY共表达的弓状神经元足以诱导贪婪的进食。在食物剥夺后递送HFD急性诱导ARC中的多巴胺（DA）释放，而在ARCAgRP/NPY神经元中缺乏Drd1表达的动物（Drd1AgRP-KO）表现出减弱的觅食和HFD的再喂养。这些结果定义了一个角色的DA输入ARC编码急性反应的食物和位置Drd1信号在ARCAgRP/NPY神经元作为一个集成的享乐和稳态神经元喂养电路。Zhang等人表明，ARC中的DA释放受到代谢状态的调节，并对可用食物的能量密度进行编码。ARC中的表达Drd 1的神经元包括ARCAgRP/NPY神经元的亚群诱导进食。ARCAgRP/NPY神经元中Drd1的基因消融减弱HFD诱导的摄食过多
Obesity comorbidities such as diabetes and cardiovascular disease are pressing public health concerns. Overconsumption of calories leads to weight gain; however, neural mechanisms underlying excessive food consumption are poorly understood. Here, we demonstrate that dopamine receptor D1 (Drd1) expressed in the agouti-related peptide/neuropeptide Y (AgRP/NPY) neurons of the arcuate hypothalamus is required for appropriate responses to a high-fat diet (HFD). Stimulation of Drd1 and AgRP/NPY co-expressing arcuate neurons is sufficient to induce voracious feeding. Delivery of a HFD after food deprivation acutely induces dopamine (DA) release in the ARC, whereas animals that lack Drd1 expression in ARCAgRP/NPY neurons (Drd1AgRP-KO) exhibit attenuated foraging and refeeding of HFD. These results define a role for the DA input to the ARC that encodes acute responses to food and position Drd1 signaling in the ARCAgRP/NPY neurons as an integrator of the hedonic and homeostatic neuronal feeding circuits. Zhang et al. show that DA release in the ARC is modulated by metabolic states and encodes the energy density of the available food. The Drd1-expressing neurons in the ARC including a subpopulation of ARCAgRP/NPY neurons induce feeding. Genetic ablation of Drd1 in ARCAgRP/NPY neurons attenuates HFD-induced hyperphagia.
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影响因子：
4.3
作者：
Coccurello R;Maccarrone M
通讯作者：
Maccarrone M
影响因子：
29
作者：
Denis RG;Joly-Amado A;Webber E;Langlet F;Schaeffer M;Padilla SL;Cansell C;Dehouck B;Castel J;Delbès AS;Martinez S;Lacombe A;Rouch C;Kassis N;Fehrentz JA;Martinez J;Verdié P;Hnasko TS;Palmiter RD;Krashes MJ;Güler AD;Magnan C;Luquet S
通讯作者：
Luquet S
影响因子：
20.3
作者：
Jais A;Brüning JC
通讯作者：
Brüning JC
影响因子：
29
作者：
Hatori M;Vollmers C;Zarrinpar A;DiTacchio L;Bushong EA;Gill S;Leblanc M;Chaix A;Joens M;Fitzpatrick JA;Ellisman MH;Panda S
通讯作者：
Panda S
影响因子：
16.6
作者：
Cavalcanti-de-Albuquerque, Joao Paulo;Bober, Jeremy;Dietrich, Marcelo O.
通讯作者：
Dietrich, Marcelo O.