Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages
Voluntary exercise attenuates obesity-associated inflammation through ghrelin expressed in macrophages
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DOI：
10.1016/j.bbrc.2011.08.117
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发表时间：
2011-09-30
影响因子：
3.1
通讯作者：
Ohno, Hideki
中科院分区：
文献类型：
--
作者：
Kizaki, Takako;Maegawa, Taketeru;Ohno, Hideki
慢性低水平炎症与肥胖和久坐不动的生活方式有关，导致代谢紊乱，如胰岛素抵抗。运动训练已被证明可以减少高脂肪饮食（HFD）引起的肥胖的慢性低水平全身性炎症。然而，介导其有益作用的分子机制尚不完全清楚。胃饥饿素是一种主要在胃中产生的肽激素，它刺激食欲并诱导生长激素的释放。除了这些众所周知的功能，最近的研究表明，胃饥饿素定位于免疫细胞并发挥抗炎作用。本研究的目的是探讨巨噬细胞中表达的胃饥饿素在自主运动训练的抗炎作用中的作用。与饲喂标准饮食的小鼠（SD小鼠）相比，饲喂HFD的小鼠（HFD小鼠）的脂肪组织中肿瘤坏死因子- α (tnf - α)、单核细胞趋化蛋白(MCP)-1和F4/80的表达增加，而饲喂HFD的小鼠（HFEx小鼠）进行自愿转轮跑时，这些炎症细胞因子的表达明显降低。高脂饮食也增加了腹腔巨噬细胞中tnf - α的表达，运动训练抑制了TNF-a表达的增加。有趣的是，胃饥饿素在腹膜巨噬细胞中的表达在HFD后降低，并在运动训练后恢复。在巨噬细胞系RAW264细胞中，siRNA抑制ghrelin表达增加TNF-a表达，lps刺激NF-kappa B活化。在胃饥饿素存在下培养的RAW264细胞中，LPS刺激TNF-a的表达被显著抑制。这些结果表明，胃饥饿素在巨噬细胞中发挥强大的抗炎作用，并作为运动训练有益效果的中介。(C) 2011爱思唯尔公司版权所有。
Chronic low-level inflammation is associated with obesity and a sedentary lifestyle, causing metabolic disturbances such as insulin resistance. Exercise training has been shown to decrease chronic low-level systemic inflammation in high-fat diet (HFD)-induced obesity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Ghrelin is a peptide hormone predominantly produced in the stomach that stimulates appetite and induces growth hormone release. In addition to these well-known functions, recent studies suggest that ghrelin localizes to immune cells and exerts an anti-inflammatory effect. The purpose of the current study was to investigate the role of ghrelin expressed in macrophages in the anti-inflammatory effects of voluntary exercise training. Expression of tumor necrosis factor-alpha (TNF-alpha), monocyte chemotactic protein (MCP)-1 and F4/80 was increased in adipose tissue from mice fed a HFD (HFD mice) compared with mice fed a standard diet (SD mice), whereas the expression of these inflammatory cytokines was markedly decreased in mice performing voluntary wheel running during the feeding of a HFD (HFEx mice). The expression of TNF-alpha was also increased in peritoneal macrophages by a HFD and exercise training inhibited the increase of TNF-a expression. Interestingly, expression of ghrelin in peritoneal macrophages was decreased by a HFD and recovered by exercise training. Suppression of ghrelin expression by siRNA increased TNF-a expression and LPS-stimulated NF-kappa B activation in RAW264 cells, which is a macrophage cell line. TNF-a expression by stimulation with LPS was significantly suppressed in RAW264 cells cultured in the presence of ghrelin. These results suggest that ghrelin exerts potent anti-inflammatory effects in macrophages and functions as a mediator of the beneficial effects of exercise training. (C) 2011 Elsevier Inc. All rights reserved.