Interplay between Peripheral and Central Inflammation in Obesity-Promoted Disorders: The Impact on Synaptic Mitochondrial Functions.

Interplay between Peripheral and Central Inflammation in Obesity-Promoted Disorders: The Impact on Synaptic Mitochondrial Functions.
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肥胖促进的疾病中外周和中枢炎症之间的相互作用:对突触线粒体功能的影响。

DOI:
10.3390/ijms21175964
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发表时间:
2020-08-19
影响因子:
5.6
通讯作者:
Mollica MP
Mollica MP
中科院分区:
生物学2区
文献类型:
--
作者:
Crispino M;Trinchese G;Penna E;Cimmino F;Catapano A;Villano I;Perrone-Capano C;Mollica MP

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由高脂饮食(HFD)消耗诱导的代谢功能障碍不仅限于参与能量代谢的器官,而且还引起影响包括中枢神经系统在内的整个身体的慢性低度全身性炎症。很长一段时间以来,大脑一直被认为是由血脑屏障保护免受全身炎症的影响,但最近的数据表明肥胖和神经退行性疾病之间存在关联。此外,肥胖相关的后果,如胰岛素和瘦素抵抗,线粒体功能障碍和活性氧(ROS)的产生,可能会预测和加速生理衰老过程的特点是全身炎症和神经系统疾病的易感性更高。在这里,我们讨论了肥胖相关的代谢功能障碍和神经炎症之间的联系,特别注意调节能量障碍和突触可塑性改变之间的相互作用的分子,例如AMP活化蛋白激酶(AMPK)和脑源性神经营养因子(BDNF)。HFD诱导的神经炎症对神经元可塑性的影响可能通过改变脑线粒体功能来介导。由于线粒体在突触区域中发挥关键作用,提供能量以支持突触可塑性并控制ROS产生,因此HFD的负面影响在突触中可能更明显。总之,它将强调HFD诱导的代谢改变,全身炎症,氧化应激,神经炎症和受损的脑可塑性是紧密相连的过程,涉及神经系统疾病的发病机制。
The metabolic dysfunctions induced by high fat diet (HFD) consumption are not limited to organs involved in energy metabolism but cause also a chronic low-grade systemic inflammation that affects the whole body including the central nervous system. The brain has been considered for a long time to be protected from systemic inflammation by the blood–brain barrier, but more recent data indicated an association between obesity and neurodegeneration. Moreover, obesity-related consequences, such as insulin and leptin resistance, mitochondrial dysfunction and reactive oxygen species (ROS) production, may anticipate and accelerate the physiological aging processes characterized by systemic inflammation and higher susceptibility to neurological disorders. Here, we discussed the link between obesity-related metabolic dysfunctions and neuroinflammation, with particular attention to molecules regulating the interplay between energetic impairment and altered synaptic plasticity, for instance AMP-activated protein kinase (AMPK) and Brain-derived neurotrophic factor (BDNF). The effects of HFD-induced neuroinflammation on neuronal plasticity may be mediated by altered brain mitochondrial functions. Since mitochondria play a key role in synaptic areas, providing energy to support synaptic plasticity and controlling ROS production, the negative effects of HFD may be more pronounced in synapses. In conclusion, it will be emphasized how HFD-induced metabolic alterations, systemic inflammation, oxidative stress, neuroinflammation and impaired brain plasticity are tightly interconnected processes, implicated in the pathogenesis of neurological diseases.
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