Accumulated preclinical literature demonstrates that hypothalamic inflammation and gliosis are underlying causal components of diet-induced obesity in rodent models. This review summarizes and synthesizes available translational data to better understand the applicability of preclinical findings to human obesity and its comorbidities. The published literature in humans includes histopathologic analyses performed postmortem and in vivo neuroimaging studies measuring indirect markers of hypothalamic tissue microstructure. Both support the presence of hypothalamic inflammation and gliosis in children and adults with obesity. Findings predominantly point to tissue changes in the region of the arcuate nucleus of the hypothalamus, although findings of altered tissue characteristics in whole hypothalamus or other hypothalamic regions also emerged. Moreover, the severity of hypothalamic inflammation and gliosis has been related to comorbid conditions, including glucose intolerance, insulin resistance, type 2 diabetes, and low testosterone levels in men, independent of elevated body adiposity. Cross-sectional findings are augmented by a small number of prospective studies suggesting that a greater degree of hypothalamic inflammation and gliosis may predict adiposity gain and worsening insulin sensitivity in susceptible individuals. In conclusion, existing human studies corroborate a large preclinical literature demonstrating that hypothalamic neuroinflammatory responses play a role in obesity pathogenesis. Extensive or permanent hypothalamic tissue remodeling may negatively affect the function of neuroendocrine regulatory circuits and promote the development and maintenance of elevated body weight in obesity and/or comorbid endocrine disorders.

中文翻译：

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下丘脑炎症和神经胶质增生对人类肥胖发病机制的意义。

积累的临床前文献表明，下丘脑炎症和神经胶质增生是啮齿动物模型中饮食诱导肥胖的潜在因果成分。本综述总结并综合了可用的转化数据，以更好地理解临床前发现对人类肥胖及其合并症的适用性。已发表的人类文献包括死后进行的组织病理学分析和测量下丘脑组织微观结构的间接标记物的体内神经影像学研究。两者都支持肥胖儿童和成人存在下丘脑炎症和神经胶质增生。研究结果主要指向下丘脑弓状核区域的组织变化，尽管也出现了整个下丘脑或其他下丘脑区域组织特征改变的发现。此外，下丘脑炎症和神经胶质增生的严重程度与合并症有关，包括葡萄糖耐受不良、胰岛素抵抗、2 型糖尿病和男性睾酮水平低，与身体肥胖无关。少量前瞻性研究加强了横断面研究结果，表明更大程度的下丘脑炎症和神经胶质增生可能预测易感个体的肥胖增加和胰岛素敏感性恶化。总之，现有的人类研究证实了大量临床前文献，证明下丘脑神经炎症反应在肥胖发病机制中发挥作用。