Fasting and prolonged food restriction differentially affect GH secretion independently of GH receptor signaling in AgRP neurons.
Fasting and prolonged food restriction differentially affect GH secretion independently of GH receptor signaling in AgRP neurons.
复制标题
禁食和长期食物限制对 GH 分泌的影响不同，与 AgRP 神经元中 GH 受体信号传导无关。
DOI：
10.1111/jne.13254
复制
发表时间：
2023
影响因子：
3.2
通讯作者：
DonatoJr,Jose
中科院分区：
文献类型：
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作者：
deSousa,MariaE;Gusmao,DanielaO;DosSantos,WillianO;Moriya,HenriqueT;deLima,FelipeF;List,EdwardO;Kopchick,JohnJ;DonatoJr,Jose
生长激素受体(GHR)在下丘脑弓状核(ARH)的神经元中大量表达，共同释放刺鼠相关蛋白(AgRP)和神经肽Y(NPY)。由于ARHAgRP/NPY神经元调节多个下丘脑-垂体-内分泌轴，这个神经元群可能通过负反馈环调节GH的分泌，特别是在食物限制期间，当ARHAgRP/NPY神经元高度活跃时。本研究旨在确定ARHAgRP/NPY神经元中的GHR信号在喂养和剥夺食物的雄性小鼠GH分泌模式中的重要性。此外，我们比较了两种不同的食物剥夺情况的效果：禁食16 h或食物限制4 天(通常食物摄入量的40%)。隔夜禁食强烈抑制基础和搏动性GH分泌。在缺乏GHR的ARHAgRP/∆神经元(AgRPNPY小鼠)中，无论是在进食状态还是在禁食状态下，GH的分泌都没有表现出与对照组小鼠的差异。相反，在对照组和 ∆GHR小鼠中，4天的限食增加了GH脉冲频率、基础GH分泌和脉搏不规则性/复杂性(由样本熵测量)，而脉动性GH分泌没有受到影响。禁食或限食对下丘脑GhrHmRNA表达无影响，但在急性禁食小鼠，Sst表达增加，但在对照组和AgRp∆GHR小鼠中，Sst表达在长时间禁食后下降。我们的发现表明，短期禁食和长期禁食对ARHAgRP/NPY神经元的GH分泌模式有不同的影响，而不依赖于GHR信号。
Growth hormone (GH) receptor (GHR) is abundantly expressed in neurons that co‐release the agouti‐related protein (AgRP) and neuropeptide Y (NPY) in the arcuate nucleus of the hypothalamus (ARH). Since ARHAgRP/NPYneurons regulate several hypothalamic–pituitary‐endocrine axes, this neuronal population possibly modulates GH secretion via a negative feedback loop, particularly during food restriction, when ARHAgRP/NPYneurons are highly active. The present study aims to determine the importance of GHR signaling in ARHAgRP/NPYneurons on the pattern of GH secretion in fed and food‐deprived male mice. Additionally, we compared the effect of two distinct situations of food deprivation: 16 h of fasting or four days of food restriction (40% of usual food intake). Overnight fasting strongly suppressed both basal and pulsatile GH secretion. Animals lacking GHR in ARHAgRP/NPYneurons (AgRP∆GHRmice) did not exhibit differences in GH secretion either in the fed or fasted state, compared to control mice. In contrast, four days of food restriction increased GH pulse frequency, basal GH secretion, and pulse irregularity/complexity (measured by sample entropy), whereas pulsatile GH secretion was not affected in both control and AgRP∆GHRmice. HypothalamicGhrhmRNA levels were unaffected by fasting or food restriction, butSstexpression increased in acutely fasted mice, but decreased after prolonged food restriction in both control and AgRP∆GHRmice. Our findings indicate that short‐term fasting and prolonged food restriction differentially affect the pattern of GH secretion, independently of GHR signaling in ARHAgRP/NPYneurons.