Currie Paul J, Mirza Aaisha, Fuld Rebecca, Park Diana, Vasselli Joseph R
Dept. of Psychology, Barnard College, Columbia University, New York, NY 10027, USA.
Am J Physiol Regul Integr Comp Physiol. 2005 Aug;289(2):R353-R358. doi: 10.1152/ajpregu.00756.2004. Epub 2005 Apr 7.
Ghrelin is a 28-amino acid acylated peptide and is the endogenous ligand for the growth hormone secretagogue receptor (GHS-R). The GHS-R is expressed in hypothalamic nuclei, including the arcuate nucleus (Arc) where it is colocalized with neuropeptide Y (NPY) neurons. In the present study, we examined the effects of ghrelin on feeding and energy substrate utilization (respiratory quotient; RQ) following direct injections into either the arcuate or the paraventricular nucleus (PVN) of the hypothalamus. Ghrelin was administered at the beginning of the dark cycle at doses of 15-60 pmol to male and female rats. In feeding studies, food intake was measured 2 and 4 h postinjection. Separate groups of rats were injected with ghrelin, and the RQ (VCO(2)/VO(2)) was measured using an open circuit calorimeter over a 4-h period. Both Arc and PVN injections of ghrelin increased food intake in male and female rats. Ghrelin also increased RQ, reflecting a shift in energy substrate utilization in favor of carbohydrate oxidation. Because these effects are similar to those observed after PVN injection of NPY, we then assessed the impact of coinjecting ghrelin with NPY into the PVN. When rats were pretreated with very low doses of ghrelin (2.5-10 pmol), NPY's (50 pmol) effects on eating and RQ were potentiated. Overall, these data are in agreement with evidence suggesting that ghrelin functions as a gut-brain endocrine hormone implicated in the regulation of food intake and energy metabolism. Our findings are also consistent with a possible interactive role of hypothalamic ghrelin and NPY systems.
胃饥饿素是一种由28个氨基酸组成的酰化肽，是生长激素促分泌素受体（GHS-R）的内源性配体。GHS-R在下丘脑核团中表达，包括弓状核（Arc），在该核团中它与神经肽Y（NPY）神经元共定位。在本研究中，我们通过直接注射到下丘脑的弓状核或室旁核（PVN）中，研究了胃饥饿素对进食和能量底物利用（呼吸商；RQ）的影响。在黑暗周期开始时，以15 - 60 pmol的剂量给雄性和雌性大鼠注射胃饥饿素。在进食研究中，在注射后2小时和4小时测量食物摄入量。将单独的几组大鼠注射胃饥饿素，并使用开路热量计在4小时内测量RQ（VCO₂/VO₂）。向弓状核和室旁核注射胃饥饿素均增加了雄性和雌性大鼠的食物摄入量。胃饥饿素还增加了RQ，这反映出能量底物利用向有利于碳水化合物氧化的方向转变。由于这些作用与向室旁核注射神经肽Y后观察到的作用相似，我们随后评估了将胃饥饿素与神经肽Y共同注射到室旁核中的影响。当用非常低剂量的胃饥饿素（2.5 - 10 pmol）预处理大鼠时，神经肽Y（50 pmol）对进食和RQ的作用增强。总体而言，这些数据与以下证据一致，即胃饥饿素作为一种肠脑内分泌激素参与食物摄入和能量代谢的调节。我们的发现也与下丘脑胃饥饿素和神经肽Y系统可能的相互作用作用一致。
