Comesaña Sara, Velasco Cristina, Ceinos Rosa M, López-Patiño Marcos A, Míguez Jesús M, Morais Sofia, Soengas José L
Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía and Centro Singular de Investigación Mariña-ECIMAT, Universidade de Vigo , Vigo , Spain.
Lucta, Innovation Division, Autonomous University of Barcelona Research Park, Bellaterra, Spain.
Am J Physiol Regul Integr Comp Physiol. 2018 Feb 1;314(2):R201-R215. doi: 10.1152/ajpregu.00283.2017. Epub 2017 Oct 18.
To assess the hypothesis of central amino acid-sensing systems involved in the control of food intake in fish, we carried out two experiments in rainbow trout. In the first one, we injected intracerebroventricularly two different branched-chain amino acids (BCAAs), leucine and valine, and assessed food intake up to 48 h later. Leucine decreased and valine increased food intake. In a second experiment, 6 h after similar intracerebroventricular treatment we determined changes in parameters related to putative amino acid-sensing systems. Different areas of rainbow trout brain present amino acid-sensing systems responding to leucine (hypothalamus and telencephalon) and valine (telencephalon), while other areas (midbrain and hindbrain) do not respond to these treatments. The decreased food intake observed in fish treated intracerebroventricularly with leucine could relate to changes in mRNA abundance of hypothalamic neuropeptides [proopiomelanocortin (POMC), cocaine- and amphetamine-related transcript (CART), neuropeptide Y (NPY), and agouti-related peptide (AgRP)]. These in turn could relate to amino acid-sensing systems present in the same area, related to BCAA and glutamine metabolism, as well as mechanistic target of rapamycin (mTOR), taste receptors, and general control nonderepressible 2 (GCN2) kinase signaling. The treatment with valine did not affect amino acid-sensing parameters in the hypothalamus. These responses are comparable to those characterized in mammals. However, clear differences arise when comparing rainbow trout and mammals, in particular with respect to the clear orexigenic effect of valine, which could relate to the finding that valine partially stimulated two amino acid-sensing systems in the telencephalon. Another novel result is the clear effect of leucine on telencephalon, in which amino acid-sensing systems, but not neuropeptides, were activated as in the hypothalamus.
为了评估鱼类中参与食物摄入控制的中枢氨基酸传感系统的假说,我们在虹鳟鱼身上进行了两项实验。在第一项实验中,我们向脑室内注射了两种不同的支链氨基酸(BCAAs),亮氨酸和缬氨酸,并在之后长达48小时的时间里评估食物摄入量。亮氨酸使食物摄入量减少,而缬氨酸使食物摄入量增加。在第二项实验中,在进行类似的脑室内处理6小时后,我们测定了与假定的氨基酸传感系统相关的参数变化。虹鳟鱼脑的不同区域存在对亮氨酸(下丘脑和端脑)和缬氨酸(端脑)有反应的氨基酸传感系统,而其他区域(中脑和后脑)对这些处理无反应。脑室内注射亮氨酸处理的鱼中观察到的食物摄入量减少可能与下丘脑神经肽[阿黑皮素原(POMC)、可卡因和苯丙胺调节转录肽(CART)、神经肽Y(NPY)和刺鼠相关肽(AgRP)]的mRNA丰度变化有关。这些变化反过来可能与同一区域存在的氨基酸传感系统有关,这些系统与支链氨基酸和谷氨酰胺代谢以及雷帕霉素的机制性靶点(mTOR)、味觉受体和一般控制非抑制性2(GCN2)激酶信号传导有关。缬氨酸处理并未影响下丘脑中的氨基酸传感参数。这些反应与在哺乳动物中所描述的反应相当。然而,在比较虹鳟鱼和哺乳动物时出现了明显差异,特别是缬氨酸具有明显的促食欲作用,这可能与缬氨酸部分刺激端脑中的两种氨基酸传感系统这一发现有关。另一个新的结果是亮氨酸对端脑有明显作用,其中氨基酸传感系统而非神经肽像在下丘脑中一样被激活。