Diurnal regulation of metabolism by Gs-alpha in hypothalamic QPLOT neurons.
Diurnal regulation of metabolism by Gs-alpha in hypothalamic QPLOT neurons.
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下丘脑QPLOT神经元中GS-Alpha代谢的昼夜调节。
DOI：
10.1371/journal.pone.0284824
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
Lang, Richard
中科院分区：
文献类型：
--
作者：
Gaitonde, Kevin P.;Andrabi, Mutahar;Burger, Courtney;D'Souza, Shane F.;Vemaraju, Shruti A.;Koritala, Bala S. C.;Smith, David;Lang, Richard
下丘脑视前区(POA)的神经元通过感觉传入和调节交感神经系统的输出来调节多种动态平衡过程，包括体温调节和睡眠。POA有一个自主的生物钟，也可能间接地从视交叉上核接收昼夜信号。我们以前定义了POA中的一个神经元子集，称为QPLOT神经元，通过分子标记(Qrfp、Ptger3、Lepr、OPN5、Tacr3)的表达来识别，这些分子标记表明对多种刺激的接受性。由于Ptger3、OPN5和Tacr3编码G蛋白偶联受体(GPCRs)，我们假设阐明这些神经元中的G蛋白信号对于理解输入在代谢调节中的相互作用是必不可少的。在这里，我们描述了QPLOT神经元中的刺激性Gs-α亚单位(GNAS)如何调节小鼠的代谢。我们在22°C(历史标准)、10°C(冷挑战)和28°C(热中性)的环境温度下使用间接量热法分析了Opn5cre；Gnasfl/fl小鼠，以评估QPLOT神经元调节新陈代谢的能力。我们观察到Opn5cre；Gnasfl/fl小鼠在28°C和22°C下夜间活动显著减少，但在能量消耗、呼吸交换或食物和水消耗方面没有总体差异。为了分析每日代谢的节律模式，我们评估了包括幅度、相位和MESOR在内的昼夜节律参数。QPLOT神经元中失去功能的GNAS导致多个代谢参数的几个微妙的节律性变化。我们观察到Opn5cre；Gnasfl/fl小鼠在22°C和10°C表现出更高的节律调整的平均能量消耗，以及夸大的呼吸交换随温度的变化。在28℃时，Opn5cre；Gnasfl/fl小鼠的能量消耗和呼吸交换阶段明显延迟。节律分析还显示，在22°C和28°C时，节律调整的食物和水摄取方式的增加有限。总之，这些数据促进了我们对GαS-视前QPLOT神经元中调节日常代谢模式的信号的理解。
Neurons in the hypothalamic preoptic area (POA) regulate multiple homeostatic processes, including thermoregulation and sleep, by sensing afferent input and modulating sympathetic nervous system output. The POA has an autonomous circadian clock and may also receive circadian signals indirectly from the suprachiasmatic nucleus. We have previously defined a subset of neurons in the POA termed QPLOT neurons that are identified by the expression of molecular markers (Qrfp, Ptger3, LepR, Opn5, Tacr3) that suggest receptivity to multiple stimuli. Because Ptger3, Opn5, and Tacr3 encode G-protein coupled receptors (GPCRs), we hypothesized that elucidating the G-protein signaling in these neurons is essential to understanding the interplay of inputs in the regulation of metabolism. Here, we describe how the stimulatory Gs-alpha subunit (Gnas) in QPLOT neurons regulates metabolism in mice. We analyzed Opn5cre; Gnasfl/fl mice using indirect calorimetry at ambient temperatures of 22°C (a historical standard), 10°C (a cold challenge), and 28°C (thermoneutrality) to assess the ability of QPLOT neurons to regulate metabolism. We observed a marked decrease in nocturnal locomotion of Opn5cre; Gnasfl/fl mice at both 28°C and 22°C, but no overall differences in energy expenditure, respiratory exchange, or food and water consumption. To analyze daily rhythmic patterns of metabolism, we assessed circadian parameters including amplitude, phase, and MESOR. Loss-of-function GNAS in QPLOT neurons resulted in several subtle rhythmic changes in multiple metabolic parameters. We observed that Opn5cre; Gnasfl/fl mice show a higher rhythm-adjusted mean energy expenditure at 22°C and 10°C, and an exaggerated respiratory exchange shift with temperature. At 28°C, Opn5cre; Gnasfl/fl mice have a significant delay in the phase of energy expenditure and respiratory exchange. Rhythmic analysis also showed limited increases in rhythm-adjusted means of food and water intake at 22°C and 28°C. Together, these data advance our understanding of Gαs-signaling in preoptic QPLOT neurons in regulating daily patterns of metabolism.
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影响因子：
3.4
作者：
McClave, SA;Lowen, CC;Goldsmith, LJ
通讯作者：
Goldsmith, LJ
DOI：
10.1073/pnas.0408268102
发表时间：
2005-05-17
影响因子：
11.1
作者：
Chen, M;Gavrilova, O;Weinstein, LS
通讯作者：
Weinstein, LS
影响因子：
25
作者：
Deboer, T;Vansteensel, MJ;Meijer, JH
通讯作者：
Meijer, JH
影响因子：
3.1
作者：
Nishimura T;Motoi M;Egashira Y;Choi D;Aoyagi K;Watanuki S
通讯作者：
Watanuki S
影响因子：
3.7
作者：
Cook, Chris;Nunn, Nicolas;Worth, Amy A.;Bechtold, David A.;Suter, Todd;Gackeheimer, Susan;Foltz, Lisa;Emmerson, Paul J.;Statnick, Michael A.;Luckman, Simon M.
通讯作者：
Luckman, Simon M.