下丘脑炎症和神经胶质瘤在人类肥胖发病中的意义。

IF 22 1区 医学 Q1 ENDOCRINOLOGY & METABOLISM Endocrine reviews Pub Date : 2023-03-04 DOI:10.1210/endrev/bnac023
Leticia E Sewaybricker, Alyssa Huang, Suchitra Chandrasekaran, Susan J Melhorn, Ellen A Schur
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引用次数: 4

摘要

积累的临床前文献表明,在啮齿动物模型中,下丘脑炎症和神经胶质瘤是饮食性肥胖的潜在原因。这篇综述总结和综合了现有的转化数据,以更好地理解临床前研究结果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组织病理学分析和体内神经成像研究,测量下丘脑组织微观结构的间接标记物。两者都支持儿童和成人肥胖患者存在下丘脑炎症和神经胶质瘤。研究结果主要指向下丘脑弓状核区域的组织变化,尽管整个下丘脑或其他下丘脑区域的组织特征也发生了变化。此外,下丘脑炎症和神经胶质瘤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型糖尿病和男性低睾酮水平,与体脂升高无关。少量前瞻性研究增强了横断面研究结果,表明下丘脑炎症和神经胶质瘤的严重程度可能预示着易感个体的肥胖增加和胰岛素敏感性恶化。总之,现有的人体研究证实了大量的临床前文献,表明下丘脑神经炎症反应在肥胖发病机制中起作用。广泛或永久性下丘脑组织重塑可能对神经内分泌调节回路的功能产生负面影响,并促进肥胖和/或共病内分泌疾病患者体重升高的发生和维持。
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The Significance of Hypothalamic Inflammation and Gliosis for the Pathogenesis of Obesity in Humans.

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.

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来源期刊
Endocrine reviews
Endocrine reviews 医学-内分泌学与代谢
CiteScore
42.00
自引率
1.00%
发文量
29
期刊介绍: Endocrine Reviews, published bimonthly, features concise timely reviews updating key mechanistic and clinical concepts, alongside comprehensive, authoritative articles covering both experimental and clinical endocrinology themes. The journal considers topics informing clinical practice based on emerging and established evidence from clinical research. It also reviews advances in endocrine science stemming from studies in cell biology, immunology, pharmacology, genetics, molecular biology, neuroscience, reproductive medicine, and pediatric endocrinology.
期刊最新文献
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