School of Biomedical Sciences, University of Queensland, St. Lucia, Brisbane, Queensland 4072, Australia.
Endocrinology. 2012 Jan;153(1):273-82. doi: 10.1210/en.2011-1681. Epub 2011 Nov 22.
Fasting results in the mobilization of adipose stores and the elevation of levels of free fatty acids (FFA). In humans, this process is driven by a release in GH. Little is known regarding the role of GH in modulating this process during early stages of fasting in the mouse. Confirmation of the role of GH in modulating FFA release in the fasting mouse is of particular importance given the frequent use of mouse models to study metabolic mechanisms. Here, we correlate the initial release of FFA throughout fasting in mice with pulsatile GH secretion. Observations illustrate the rapid release of FFA in response to food withdrawal. This does not correlate with a rise in GH secretion. Rather, we observed a striking loss in pulsatile secretion of GH throughout the first 6 h of fasting, suggesting that GH does not modulate the initial release of FFA in the mouse in response to fasting. This was confirmed in GH receptor knockout mice, in which we observed a robust fasting-induced rise in FFA. We further illustrate the dynamic relationship between the orexigenic and anorexigenic hormones ghrelin and leptin during fasting in the mouse. Our findings show an initial suppression of leptin and the eventual rise in circulating levels of acyl-ghrelin with fasting. However, altered acyl-ghrelin and leptin secretion occurs well after the rise in FFA and the suppression of GH secretion. Consequently, we conclude that although acyl-ghrelin and leptin may modulate the physiological response to drive food intake, these changes do not contribute to the initial loss of pulsatile GH secretion. Rather, it appears that the suppression of GH secretion in fasting may occur in response to an elevation in fasting levels of FFA or physiological stress. Observations highlight a divergent role for GH in modulating FFA release between man and mouse.
禁食导致脂肪储存的动员和游离脂肪酸 (FFA) 水平的升高。在人类中，这一过程是由 GH 的释放驱动的。关于 GH 在调节禁食早期小鼠这一过程中的作用知之甚少。鉴于经常使用小鼠模型来研究代谢机制，确认 GH 在调节禁食小鼠 FFA 释放中的作用尤为重要。在这里，我们将小鼠禁食过程中 FFA 的初始释放与 GH 脉冲分泌相关联。观察结果表明，FFA 会迅速释放以响应食物剥夺。这与 GH 分泌的增加无关。相反，我们观察到在禁食的前 6 小时内，GH 脉冲分泌明显丧失，这表明 GH 不会调节禁食时小鼠 FFA 的初始释放。这在 GH 受体敲除小鼠中得到了证实，我们观察到在禁食时 FFA 会强烈增加。我们进一步说明了在禁食期间，食欲刺激激素 ghrelin 和厌食激素 leptin 之间的动态关系。我们的研究结果表明，在禁食期间，leptin 最初被抑制，随后循环中酰基-ghrelin 的水平升高。然而，酰基-ghrelin 和 leptin 分泌的改变发生在 FFA 升高和 GH 分泌抑制之后。因此，我们得出结论，尽管酰基-ghrelin 和 leptin 可能调节生理反应以驱动食物摄入，但这些变化并不是导致 GH 脉冲分泌初始丧失的原因。相反，禁食时 GH 分泌的抑制似乎是对 FFA 或生理应激水平升高的反应。这些观察结果强调了 GH 在调节 FFA 释放方面在人和小鼠之间的不同作用。
