Department of Endocrinology and Metabolism, Amsterdam University Medical Center (UMC), University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Laboratory of Endocrinology, Amsterdam University Medical Center (UMC), University of Amsterdam, Amsterdam Gastroenterology & Metabolism, 1105 AZ Amsterdam, The Netherlands.
Int J Mol Sci. 2021 Mar 19;22(6):3141. doi: 10.3390/ijms22063141.
The prevalence of obesity has increased rapidly in recent years and has put a huge burden on healthcare worldwide. Obesity is associated with an increased risk for many comorbidities, such as cardiovascular diseases, type 2 diabetes and hypertension. The hypothalamus is a key brain region involved in the regulation of food intake and energy expenditure. Research on experimental animals has shown neuronal loss, as well as microglial activation in the hypothalamus, due to dietary-induced obesity. Microglia, the resident immune cells in the brain, are responsible for maintaining the brain homeostasis and, thus, providing an optimal environment for neuronal function. Interestingly, in obesity, microglial cells not only get activated in the hypothalamus but in other brain regions as well. Obesity is also highly associated with changes in hippocampal function, which could ultimately result in cognitive decline and dementia. Moreover, changes have also been reported in the striatum and cortex. Microglial heterogeneity is still poorly understood, not only in the context of brain region but, also, age and sex. This review will provide an overview of the currently available data on the phenotypic differences of microglial innate immunity in obesity, dependent on brain region, sex and age.
近年来，肥胖症的患病率迅速上升，给全球医疗保健带来了巨大负担。肥胖与许多合并症的风险增加有关，如心血管疾病、2 型糖尿病和高血压。下丘脑是参与调节食物摄入和能量消耗的关键脑区。对实验动物的研究表明，由于饮食诱导的肥胖，下丘脑中存在神经元丧失和小胶质细胞激活。小胶质细胞是大脑中的固有免疫细胞，负责维持大脑内环境平衡，从而为神经元功能提供最佳环境。有趣的是，在肥胖症中，小胶质细胞不仅在下丘脑中被激活，在其他脑区也被激活。肥胖症还与海马功能的变化高度相关，这可能最终导致认知能力下降和痴呆。此外，纹状体和皮质也有变化的报道。小胶质细胞异质性的研究还很不充分，不仅在脑区方面，而且在年龄和性别方面也是如此。本综述将概述目前关于肥胖症中小胶质细胞固有免疫表型差异的相关数据，这些差异取决于脑区、性别和年龄。
