Department of Physiology (Q.W., M.B.L., R.S., J.A.B., A.R., S.H.L., Z.B.A.), Monash University, Clayton, Victoria 3800, Australia; and Traditional Chinese Medicine Department (Q.W.), Peking Union Medical College Hospital, No.1 Shuaifuyuan Wangfujing, Dongcheng District, Beijing, China 100730.
Endocrinology. 2014 Mar;155(3):840-53. doi: 10.1210/en.2013-1831. Epub 2014 Jan 9.
In this study we examined fasted and refed cfos activation in cortical, brainstem, and hypothalamic brain regions associated with appetite regulation. We examined a number of time points during refeeding to gain insight into the temporal pattern of neuronal activation and changes in endocrine parameters associated with fasting and refeeding. In response to refeeding, blood glucose and plasma insulin returned to basal levels within 30 minutes, whereas plasma nonesterified fatty acids and leptin returned to basal levels after 1 and 2 hours, respectively. Within the hypothalamic arcuate nucleus (ARC), fasting increased cfos activation in ∼25% of neuropeptide Y neurons, which was terminated 1 hour after refeeding. Fasting had no effect on cfos activation in pro-opiomelanocortin neurons; however, 1 and 2 hours of refeeding significantly activated ∼20% of ARC pro-opiomelanocortin neurons. Acute refeeding (30, 60, and 120 minutes), but not fasting, increased cfos activation in the nucleus accumbens, the cingulate cortex (but not the insular cortex), the medial and lateral parabrachial nucleus, the nucleus of the solitary tract, the area postrema, the dorsal raphe, and the ventromedial nucleus of the hypothalamus. After 6 hours of refeeding, cfos activity was reduced in the majority of these regions compared with that at earlier time points. Our data indicate that acute refeeding, rather than long-term fasting, activates cortical, brainstem, and hypothalamic neural circuits associated with appetite regulation and reward processing. Although the hypothalamic ARC remains a critical sensory node detecting changes in the metabolic state and feedback during fasting and acute refeeding, our results also reveal the temporal pattern in cfos activation in cortical and brainstem areas implicated in the control of appetite and body weight regulation.
在这项研究中，我们检查了与食欲调节相关的皮质、脑干和下丘脑脑区在禁食和再进食时的 c-fos 激活。我们检查了再进食过程中的多个时间点，以深入了解与禁食和再进食相关的神经元激活和内分泌参数变化的时间模式。再进食后，血糖和血浆胰岛素在 30 分钟内恢复到基础水平，而血浆非酯化脂肪酸和瘦素则分别在 1 小时和 2 小时后恢复到基础水平。在下丘脑弓状核（ARC）中，禁食使约 25%的神经肽 Y 神经元的 c-fos 激活增加，而在再进食 1 小时后终止。禁食对前阿黑皮素原神经元的 c-fos 激活没有影响；然而，1 小时和 2 小时的再进食显著激活了约 20%的 ARC 前阿黑皮素原神经元。急性再进食（30、60 和 120 分钟），而不是禁食，增加了伏隔核、扣带回皮质（但不是岛叶皮质）、中脑和外侧臂旁核、孤束核、最后区、中缝背核和下丘脑腹内侧核的 c-fos 激活。与早期时间点相比，再进食 6 小时后，大多数区域的 c-fos 活性降低。我们的数据表明，急性再进食而不是长期禁食会激活与食欲调节和奖励处理相关的皮质、脑干和下丘脑神经回路。虽然下丘脑 ARC 仍然是一个关键的感觉节点，用于检测代谢状态的变化和在禁食和急性再进食期间的反馈，但我们的结果也揭示了与食欲和体重调节控制相关的皮质和脑干区域中 c-fos 激活的时间模式。
