Stathori Galateia, Vlahos Nikolaos F, Charmandari Evangelia, Valsamakis Georgios
Center for the Prevention and Management of Overweight and Obesity, Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, Medical School, National and Kapodistrian University of Athens, 'Aghia Sophia' Children's Hospital, 11527 Athens, Greece.
Second Department of Obstetrics and Gynecology, Medical School, National and Kapodistrian University of Athens, 'Aretaieion' University Hospital, 11528 Athens, Greece.
Int J Mol Sci. 2025 Apr 25;26(9):4047. doi: 10.3390/ijms26094047.
Obesity is a multifactorial condition linked to severe health complications, including cardiovascular diseases and endothelial dysfunction. Both obesity and high-fat diets (HFDs) are strongly associated with neuroinflammation, particularly in the hypothalamus. The autonomic nervous system (ANS), which controls involuntary physiological processes, is critical for maintaining cardiovascular health, and its dysfunction is implicated in endothelial disorders. With its homeostatic control centers located in the hypothalamus and brainstem, a crucial question arises: could obesity- and HFD-induced neuroinflammation disrupt central ANS structures, leading to ANS dysfunction and subsequent endothelial disorders? This review examined whether neuroinflammation caused by obesity and HFD contributes to endothelial dysfunction through the dysregulation of the ANS. Our analysis revealed that hypothalamic inflammation linked to obesity and an HFD is associated with sympathetic hyperactivity and endothelial disorders. Identified molecular mechanisms include the influence of inflammatory cytokines, activation of the NF-κB/IKK-β pathway, microglial activation mediated by angiotensin II, circulating mitochondria triggering cGAS activation, and the stimulation of the TLR4 pathway. Our findings suggest that hypothalamic inflammation may play a central role in the interplay between obesity/an HFD, ANS dysfunction, and endothelial disorders.
肥胖是一种与严重健康并发症相关的多因素病症，这些并发症包括心血管疾病和内皮功能障碍。肥胖和高脂饮食（HFD）均与神经炎症密切相关，尤其是在下丘脑。自主神经系统（ANS）控制着非自主生理过程，对维持心血管健康至关重要，其功能障碍与内皮疾病有关。由于其稳态控制中心位于下丘脑和脑干，因此出现了一个关键问题：肥胖和高脂饮食诱导的神经炎症是否会破坏中枢自主神经系统结构，导致自主神经系统功能障碍及随后的内皮疾病？这篇综述探讨了肥胖和高脂饮食引起的神经炎症是否通过自主神经系统的失调导致内皮功能障碍。我们的分析表明，与肥胖和高脂饮食相关的下丘脑炎症与交感神经活动亢进和内皮疾病有关。已确定的分子机制包括炎性细胞因子的影响、NF-κB/IKK-β 途径的激活、血管紧张素 II 介导的小胶质细胞激活、循环线粒体触发 cGAS 激活以及 TLR4 途径的刺激。我们的研究结果表明，下丘脑炎症可能在肥胖/高脂饮食、自主神经系统功能障碍和内皮疾病之间的相互作用中起核心作用。
