Cholinergic neurons in the hypothalamus and dorsal motor nucleus of the vagus are directly responsive to growth hormone.

Cholinergic neurons in the hypothalamus and dorsal motor nucleus of the vagus are directly responsive to growth hormone.
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DOI:
10.1016/j.lfs.2020.118229
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发表时间:
2020-10-15
期刊:
影响因子:
6.1
通讯作者:
Donato J Jr
Donato J Jr
中科院分区:
医学2区
文献类型:
--
作者:
Quaresma PGF;Teixeira PDS;Wasinski F;Campos AMP;List EO;Kopchick JJ;Donato J Jr

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胆碱能神经元分布于含有生长激素(GH)反应细胞的脑区。我们确定胆碱能神经元是否直接响应生长激素,以及在胆碱乙酰转移酶(ChAT)表达细胞中删除生长激素受体(GHR)的代谢后果。小鼠接受急性GH注射,以检测共表达ChAT和磷酸化STAT5 (pSTAT5)的神经元,pSTAT5是GH应答细胞的一种公认的标记物。在生理研究中,制备了只在chat表达细胞中携带GHR消融的小鼠,并测定了在进食常规食物或高脂肪饮食(HFD)时能量和葡萄糖稳态可能发生的变化。下丘脑弓状核(60%)和背内侧核(84%)的大部分胆碱能神经元直接对GH有反应。迷走神经背运动核中约34%的神经节前副交感神经元也表现出gh诱导的pSTAT5。GHR ChAT敲除小鼠中,GHR诱导的这些ChAT神经元中的pSTAT5缺失。携带chat特异性GHR缺失的小鼠,无论是在食物中还是在HFD中,体重、体脂、瘦体重、食物摄入、能量消耗、呼吸商、动态活动、血清瘦素水平、葡萄糖耐量、胰岛素敏感性和对2-脱氧-d -葡萄糖的代谢反应都没有显著变化。然而,ChAT神经元GHR缺失导致HFD小鼠下丘脑Pomc mRNA水平下降。调节代谢的胆碱能神经元直接响应生长激素,尽管这些细胞中的GHR信号不是能量和葡萄糖稳态所必需的。因此,生长激素作用于胆碱能神经元的生理重要性仍然需要确定。
Cholinergic neurons are distributed in brain areas containing growth hormone (GH)-responsive cells. We determined if cholinergic neurons are directly responsive to GH and the metabolic consequences of deleting the GH receptor (GHR) specifically in choline acetyltransferase (ChAT)-expressing cells. Mice received an acute injection of GH to detect neurons co-expressing ChAT and phosphorylated STAT5 (pSTAT5), a well-established marker of GH-responsive cells. For the physiological studies, mice carrying ablation of GHR exclusively in ChAT-expressing cells were produced and possible changes in energy and glucose homeostasis were determined when consuming regular chow or high-fat diet (HFD). The majority of cholinergic neurons in the arcuate nucleus (60%) and dorsomedial nucleus (84%) of the hypothalamus are directly responsive to GH. Approximately 34% of pre-ganglionic parasympathetic neurons in the dorsal motor nucleus of the vagus also exhibited GH-induced pSTAT5. GH-induced pSTAT5 in these ChAT neurons was absent in GHR ChAT knockout mice. Mice carrying ChAT-specific GHR deletion, either in chow or HFD, did not exhibit significant changes in body weight, body adiposity, lean body mass, food intake, energy expenditure, respiratory quotient, ambulatory activity, serum leptin levels, glucose tolerance, insulin sensitivity and metabolic responses to 2-deoxy-D-glucose. However, GHR deletion in ChAT neurons caused decreased hypothalamic Pomc mRNA levels in HFD mice. Cholinergic neurons that regulate the metabolism are directly responsive to GH, although GHR signaling in these cells is not required for energy and glucose homeostasis. Thus, the physiological importance of GH action on cholinergic neurons still needs to be identified.
DOI: 10.1530/jme-19-0158
发表时间: 2020-01-01
影响因子: 3.5
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发表时间: 2017-01-01
影响因子: 3.1
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