Hospital Infantil Universitario Niño Jesús, Department of Endocrinology, Instituto de Investigación La Princesa, Universidad Autónoma de Madrid and Centro de Investigación Biomédica en Red (CIBER) de la Fisiopatología de la Obesidad y Nutrición, Instituto de Salud Carlos III, 28009 Madrid, Spain.
Endocrinology. 2014 Aug;155(8):2868-80. doi: 10.1210/en.2014-1074. Epub 2014 May 21.
Ghrelin is an endogenous hormone that stimulates appetite and adipose tissue accrual. Both the acylated (AG) and non-acylated (DAG) isoforms of this hormone are also reported to exert anti-inflammatory and protective effects systemically and in the central nervous system. As inflammatory processes have been implicated in obesity-associated secondary complications, we hypothesized that this natural appetite stimulator may protect against negative consequences resulting from excessive food intake. Adult male Wistar rats were treated icv (5 μg/day) with AG, DAG, the ghrelin mimetic GH-releasing peptide (GHRP)-6, AG, and pair-fed with controls (AG-pf) or saline for 14 days. Regardless of food intake AG increased visceral adipose tissue (VAT) and decreased circulating cytokine levels. However, AG reduced cytokine production in VAT only in rats fed ad libitum. Hypothalamic cytokine production was increased in AG-treated rats fed ad libitum and by DAG, but intracellular inflammatory signaling pathways associated with insulin and leptin resistance were unaffected. Gliosis was not observed in response to any treatment as glial markers were either reduced or unaffected. AG, DAG, and GHRP-6 stimulated production of hypothalamic insulin like-growth factor I that is involved in cell protective mechanisms. In hypothalamic astrocyte cell cultures AG decreased tumor necrosis factorα and DAG decreased interleukin-1β mRNA levels, suggesting direct anti-inflammatory effects on astrocytes. Thus, whereas ghrelin stimulates food intake and weight gain, it may also induce mechanisms of cell protection that help to detour or delay systemic inflammatory responses and hypothalamic gliosis due to excess weight gain, as well as its associated pathologies.
胃饥饿素是一种内源性激素，它能刺激食欲和脂肪组织的积累。这种激素的酰化（AG）和非酰化（DAG）两种形式也被报道具有抗炎和保护作用，无论是在全身还是中枢神经系统。由于炎症过程与肥胖相关的继发性并发症有关，我们假设这种天然的食欲刺激物可能有助于预防过度进食带来的负面影响。成年雄性 Wistar 大鼠通过脑室内（icv）给予 AG、DAG、胃饥饿素模拟肽 GH 释放肽（GHRP）-6、AG 治疗，或与对照组（AG-pf）或生理盐水进行配对喂养，持续 14 天。无论食物摄入量如何，AG 均增加了内脏脂肪组织（VAT），降低了循环细胞因子水平。然而，只有在自由进食的大鼠中，AG 才会减少 VAT 中的细胞因子产生。在自由进食的 AG 处理大鼠和 DAG 处理大鼠中，下丘脑细胞因子的产生增加，但与胰岛素和瘦素抵抗相关的细胞内炎症信号通路不受影响。由于胶质细胞标志物减少或不受影响，没有观察到任何治疗引起的神经胶质增生。AG、DAG 和 GHRP-6 刺激了下丘脑胰岛素样生长因子 I 的产生，该因子参与细胞保护机制。在下丘脑星形胶质细胞培养物中，AG 降低了肿瘤坏死因子α的表达，DAG 降低了白细胞介素-1β的 mRNA 水平，这表明 AG 对星形胶质细胞具有直接的抗炎作用。因此，尽管胃饥饿素刺激了食物摄入和体重增加，但它也可能诱导细胞保护机制，有助于迂回或延迟由于体重过度增加以及与之相关的病理学引起的全身炎症反应和下丘脑神经胶质增生。
