Department of Physiological Sciences, Institute of Biological and Health Sciences, Federal Rural University of Rio de Janeiro, Seropédica, Rio de Janeiro, Brazil.
Department of Physiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
J Neuroendocrinol. 2023 Nov;35(11):e13334. doi: 10.1111/jne.13334. Epub 2023 Sep 4.
In addition to being recognised for involvement in cardiovascular control and hydromineral balance, the renin-angiotensin system (RAS) has also been associated with the neuroendocrine control of energy balance. One of the main brain sites for angiotensin II (ANG II)/type 1 receptor (AT R) signalling is the subfornical organ (SFO), a circumventricular organ related to the control of autonomic functions, motivated behaviours and energy metabolism. Thus, we hypothesised that circulating ANG II may act on the SFO AT R receptors to integrate metabolic and hydromineral balance. We evaluated whether food deprivation can modulate systemic RAS activity and Agrt1a brain expression, and if ANG II/AT R signalling influences the hypothalamic expression of mRNAs encoding neuropeptides and food and water ingestion in fed and fasted Wistar rats. We found a significant increase in both ANG I and ANG II plasma levels after 24 and 48 h of fasting. Expression of Agrt1a mRNA in the SFO and paraventricular nucleus (PVN) also increased after food deprivation for 48 h. Treatment of fasted rats with low doses of losartan in drinking water attenuated the decrease in glycemia and meal-associated water intake without changing the expression in PVN or arcuate nucleus of mRNAs encoding selected neuropeptides related to energy homeostasis control. These findings point to a possible role of peripheral ANG II/SFO-AT R signalling in the control of refeeding-induced thirst. On the other hand, intracerebroventricular losartan treatment decreased food and water intake over dark time in fed but not in fasted rats.
除了参与心血管控制和水盐平衡外,肾素-血管紧张素系统 (RAS) 也与能量平衡的神经内分泌控制有关。血管紧张素 II (ANG II)/型 1 受体 (AT R) 信号的主要脑区之一是穹窿下器官 (SFO),这是一个与自主功能、动机行为和能量代谢控制有关的室周器官。因此,我们假设循环中的 ANG II 可能作用于 SFO AT R 受体,以整合代谢和水盐平衡。我们评估了禁食是否可以调节全身 RAS 活性和 Agrt1a 脑表达,以及 ANG II/AT R 信号是否会影响下丘脑编码神经肽和食物及水摄入的 mRNA 的表达,以评估在进食和禁食的 Wistar 大鼠中。我们发现,禁食 24 和 48 小时后,血浆中 ANG I 和 ANG II 的水平均显著升高。SFO 和室旁核 (PVN) 中 Agrt1a mRNA 的表达在禁食 48 小时后也增加。在饮用水中给予低剂量氯沙坦治疗禁食大鼠,可减轻血糖下降和与摄食相关的水摄入,但不改变与能量平衡控制相关的选定神经肽编码的 mRNAs 在 PVN 或弓状核中的表达。这些发现表明,外周 ANG II/SFO-AT R 信号在控制再喂养诱导的口渴中可能发挥作用。另一方面,侧脑室给予氯沙坦治疗可减少喂食大鼠在黑暗时间的摄食和饮水,但不能减少禁食大鼠的摄食和饮水。